[PHYSIO]LEC_002_MEMBRANE TRANSPORT, NERVE POTENTIAL, ACTION POTENTIAL.pdf

(002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 OUTLINE B....

(002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 OUTLINE B. FUNCTION OF THE CELL MEMBRANE I. CELL MEMBRANE Barrier against movement or prevents passage water A. Composition molecules or water-soluble substance (e.g. Ions, glucose, B. Function urea, other polar substance) II. CELL MEMBRANE PROTEINS Medium for Passage for lipids and lipid soluble molecules A. Integral proteins (e.g. Carbon dioxide, nitrogen, oxygen, alcohol) B. Peripheral proteins III. CELL MEMBRANE TRANSPORT CELL MEMBRANE PROTEINS A. Passive diffusion B. Factors that affect net rate of diffusion 1. Integral Proteins C. Osmosis D. Active transport Occupy the whole thickness IV. MEMBRANE POTENTIAL Serve as membrane transporters V. ACTION POTENTIAL I. Types of Integral Proteins i. Channel /Pores ii. Carrier CELL MEMBRANE iii. Pump 2. Peripheral Proteins CELL MEMBRANE - also known as “plasma membrane” Attached to either Inside (Enzyme) or Outside − Covers the outside of every cell of the body. (Receptor) of the cell the membrane − It is Elastic, Dynamic and Semipermeable Can also be attached to integral proteins − Very selective on the substances or molecules or ions that Protein Channels will pass Selective permeable to certain substances Opened or closed by Gates A. APPROXIMATE COMPOSITION Types of Gates Proteins: 55% 1. Voltage gated - regulated by electrical signal Carbohydrate: 3% Ex. Na+ and K+ gates Lipids: 42% 2. Ligand gated - regulated by chemicals o Phospholipid Ex. Acetylcholine channel o Cholesterol Pores o Other lipids Cell membrane proteins that form open tubes through the o Sphingolipid (Nerves cells are usually consist of membrane that are always open sphingolipids) Diameter and electrical charges provide selectivity the only Structure of the Cell Membrane is a Phospholipid bilayer Composed permits only certain mol to pass thru of: Aquaporin Protein pores that are water channels only permit rapid Hydrophilic head- which interacts with Aqueous environment passage pf water which are the ECF (Extracellular fluid) and the ICF (Intracellular Excludes other molecules and hydrated ions since fluid) aquaporins are too small for other substance or hydrated Hydrophobic tail - which repels water and nonpolarized and ions consist of free fatty acids --Highly sensitive barrier Carrier proteins Transport substance which could penetrate the lipid bilayer. Through diffusion or against electro chemical gradient called active transport: 1. Facilitated diffusion - No energy/ATP required 2. Active transport - Requires energy/ATP which uses a carrier CELL MEMBRANE TRANSPORT A. PASSIVE TRANSPORT Is the net movement of material from an area of high concentration to an area with lower concentration Describe as moving solutes down a concentration gradient Does not requires ATP Usually follows along the electro chemical gradient Figure 1. Structure of the cell membrane “Gradient” is any difference of electrical capabilities or concentration Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 Types of Passive Transport: Conversely, the rate at which molecules diffuse outward is proportional to their concentration inside the membrane. 1. SIMPLE DIFFUSION No carrier and does not need energy 2. Nernst potential - diffusion potential level across a membrane Occur through the interstices of the lipid bilayer if the that exactly opposes the net diffusion of a particular ion through substance is lipid soluble the membrane Can pass through the watery channels if they water soluble like sodium or small or can pass through both facilities If an electrical potential is applied across the membrane, the electrical charges of the ions cause them to move through the Rate of Diffusion - As the concentration of substance increases the membrane even though no concentration difference exists to rate of diffusion also rises proportionately cause movement. The concentration of negative ions is the same on both sides of the membrane, if a positive charge has been 2. FACILITATED DIFFUSION applied to the right side of the membrane and a negative charge Needs a specific carrier has been applied to the left, creating an electrical gradient across Substance are transported by entering the pore and binding the membrane. to a “receptor” on the inside of the protein carrier. The molecule becomes bound. In a fraction of a second, a The positive charge attracts the negative ions, whereas the conformational or chemical change occurs in the carrier negative charge repels them. Therefore, net diffusion occurs from protein, so the pore now opens to the opposite side of the left to right. After some time, large quantities of negative ions have membrane. Because the binding force of the receptor is moved to the right, in which a concentration difference of the ions weak, the thermal motion of the attached molecule causes it has developed in the direction opposite to the electrical potential to break away and be released on the opposite side of the difference. membrane. Rate of Diffusion The concentration difference now tends to move the ions to the Cannot raise greater than the Vmax level left, while the electrical difference tends to move them to the right. When the concentration difference rises high enough, the two The rate at which molecules can be transported by the effects balance each other. mechanism can never be greater than the rate at which the carrier protein molecule can undergo change back and forth between its two states. Figure 3. The effect of electrical potential difference affecting negative ions Figure 2. The effect of concentration of a substance on the rate of -At body temperature electrical difference that will balance a given diffusion through a membrane by simple diffusion and facilitated concentration difference of a univalent ions (ex. Sodium, diffusion. Potassium) can determine by the formula called the Nernst equation: FACTORS THAT AFFECT THE NET RATE OF DIFFUSION 1. Concentration Difference (concentration outside minus concentration inside) Is directly proportional to the net rate of diffusion The rate at which the substance diffuses inward is proportional to the concentration of molecules on the outside because this concentration determines how many molecules strike the outside of the membrane each second. Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 3. Pressure Difference Osmolarity High pressure to low pressure. Is the osmolar concentration expressed as osmoles per liter of Pressure means the sum of all the forces of the different solution rather than osmoles per kilogram of water. molecules striking a unit surface area at a given instant. It is osmoles per kilogram of water (osmolality) that determines Therefore, having a higher pressure on one side of a osmotic pressure, for dilute solutions such as those in the body, membrane than on the other side means that the sum of all the quantitative differences between osmolarity and osmolality the forces of the molecules striking the channels on that side are less than 1 percent) of the membrane is greater than on the other side. In most Far more practical to measure osmolarity than osmolality, instances, this is caused by greater numbers of molecules measuring osmolarity is the usual practice in almost all striking the membrane per second on one side than on the physiological studies. other side. The result is that increased amounts of energy are available to cause net movement of molecules from the high- B. ACTIVE TRANSPORT pressure side toward the low-pressure side. Makes movement of ions or other substance across a 3. OSMOSIS membrane in combination with a carrier protein. Is the simple diffusion of water from a high concentration of Carrier protein causes the substance to move against the water to low concentration of water or it is the simple diffusion energy gradient of water from a low concentration of solute to high Transport is uphill from a low concentration to high concentration of solute concentration It is measured using osmotic pressure. Needs ATP/Energy Types Of Active Transport Using A Carrier (According to the source Osmotic pressure of the energy used) This is the pressure needed to stop osmosis. Depends on the number or molar concentration of molecules it A. PRIMARY ACTIVE TRANSPORT does not depend of the size molecules Energy is usually derived from the breakdown of ATP or some At normal body temperature, 37°C, a concentration of 1 high other high energy phosphate compound milliosmole per liter concentration is equivalent to 19.3 mm Hg osmotic pressure. Multiplying this value by the 300-milliosmolar Examples of Primary Active Transport concentration of the body fluids gives a total calculated osmotic 1. Sodium-Potassium ATPase Pump (Na+-K+ Pump) pressure of the body fluids of 5790 mm Hg. The measured value for this, however, averages only about 5500 mm Hg. The reason Most abundant can be seen in almost all cells for this difference is that many of the ions in the body fluids, such Pump sodium out and pumps potassium in as sodium and chloride ions, are highly attracted to one another; Responsible for maintaining the sodium and potassium consequently, they cannot move entirely unrestrained in the concentration differences across the cell membrane fluids and create their full osmotic pressure potential. As well as for establishing a negative electrical voltage inside the cells Osmolality Three Specific Features That Are Important For The Functioning Of Osmosis caused by a mole The Pump Term use to express concentration of a solution in terms of 1. It has three binding sites for sodium ions on the portion of the number of particles protein that protrudes to the inside of the cell. Osmole is the unit use in place of gram 2. It has two binding sites for potassium ions on the outside. 1 osmole is 1 gram per molecular weight (moles) of an 3. The inside portion of this protein near the sodium binding sites osmotically active solute has adenosine triphosphatase (ATPase) activity. Not all solutes are osmotically active 1-gram molecular weight of glucose, is equal to 1 osmole of Mechanism of the Pump glucose because glucose does not dissociate into ions. If a solute dissociates into two ions, 1-gram molecular weight of When two potassium ions bind on the outside of the carrier protein and the solute (sodium chloride) will become 2 osmoles because the three sodium ions bind on the inside, the ATPase function of the number of osmotically active particles is now twice as great as protein becomes activated. Activation of the ATPase function leads to is the case for the non-dissociated solute cleavage of one molecule of ATP, splitting it to adenosine diphosphate Solution that has 1 osmole of solute dissolved in each kilogram (ADP) and liberating a high-energy phosphate bond of energy. This of water is said to have an osmolality of 1 osmole per kilogram, liberated energy is then believed to cause a chemical and and a solution that has 1/1000 osmole dissolved per kilogram conformational change in the protein carrier molecule, extruding the has an osmolality of 1 milliosmole per kilogram. three sodium ions to the outside and the two potassium ions to the The normal osmolality of the extracellular and intracellular fluids inside. is about 300 milliosmoles per kilogram of water. Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 In each of these instances, the carrier protein penetrates the membrane and functions as an enzyme ATPase, with the same capability to cleave ATP as the ATPase of the sodium carrier protein. The difference is that this protein has a highly specific binding site for calcium instead of for sodium. 3. Hydrogen Ion ATPase Pump (Hydrogen Ion Pump) Primary active transport of hydrogen ions is important at two places in the body: a. In the Gastric Glands of The Stomach -the deep-lying parietal cells have the most potent primary active mechanism for Figure 4. The postulated mechanism of the sodium-potassium pump. transporting hydrogen ions of any part of the body. This mecha- ADP, adenosine diphosphate; ATP, adenosine triphosphate; Pi, nism is the basis for secreting hydrochloric acid in stomach digestive secretions. At the secretory ends of the gastric gland phosphate ion. parietal cells, the hydrogen ion concentration is increased as Functions of the Pump much as a million-fold and then is released into the stomach along with chloride ions to form hydrochloric acid a. Controls cells volume - Inside the cell are large numbers of proteins and other organic molecules that cannot escape from the cell. Most of these proteins and other organic molecules b. In the Late Distal Tubules and Cortical Collecting Ducts of are negatively charged and therefore attract large numbers of The Kidneys- In the renal tubules, special intercalated cells potassium, sodium, and other positive ions as well. All these found in the late distal tubules and cortical collecting ducts also molecules and ions then cause osmosis of water to the transport hydrogen ions by primary active transport. In this case, large amounts of hydrogen ions are secreted from the blood into interior of the cell. The cell will swell indefinitely until it bursts the urine for the purpose of eliminating excess hydrogen ions if the process is left unchecked. from the body fluids. The hydrogen ions can be secreted into the The normal mechanism for preventing this outcome is the urine against a concentration gradient of about 900-fold Na+-K+ pump. Note again that this device pumps three Na+ ions to the outside of the cell for every two K+ ions pumped B. SECONDARY ACTIVE TRANSPORT to the interior. Also, the membrane is far less permeable to No direct coupling of ATP instead it relies upon the sodium ions than it is to potassium ions, and thus once the electrochemical gradient of the electrochemical potential sodium ions are on the outside, they have a strong tendency difference created by the pumping of ions in and out of the cell to stay there. This process thus represents a net loss of ions Energy is from Primary Transport out of the cell, which initiates osmosis of water out of the cell as well. Types of Secondary Transport b. Makes Na+ more prevalent in the ECF and K+ more prevalent in the ICF 1. Co-transport- When sodium ions are transported out of cells by c. Electrogenic Nature of the Na+-K+ Pump- Na+-K+ pump primary active transport, a large concentration gradient of sodium moves three Na+ ions to the exterior for every two K+ ions ions across the cell membrane usually develops, with high that are moved to the interior means that a net of one positive concentration outside the cell and low concentration inside. This charge is moved from the interior of the cell to the exterior for gradient represents a storehouse of energy because the excess each cycle of the pump. This action creates positivity outside sodium outside the cell membrane is always attempting to diffuse the cell but results in a deficit of positive ions inside the cell; to the interior. Under appropriate conditions, this diffusion energy that is, it causes negativity on the inside. Therefore, the Na+- of sodium can pull other substances along with the sodium K+ pump is said to be electrogenic because it creates an through the cell membrane. electrical potential across the cell membrane -a coupling mechanism is required for sodium to pull another substance along with it, it is achieved by another carrier protein in 2. Calcium ATPase Pump (Calcium Pump) the cell membrane. Carrier serves as an attachment point for both the sodium ion and the substance to be co-transported. Once Calcium ions are normally maintained at an extremely low they both are attached, the energy gradient of the sodium ion concentration in the intracellular cytosol of virtually all cells in the body, causes both the sodium ion and the other substance to be at a concentration about 10,000 times less than that in the extracellular transported together to the interior of the cell. fluid. Maintained by two primary active transport calcium pumps: 2. Counter-transport- sodium ions again attempt to diffuse to the One pump in the cell membrane, pumps calcium to the outside of interior of the cell because of their large concentration gradient. the cell. However, this time, the substance to be transported is on the The other pumps calcium ions into one or more of the intracellular inside of the cell and must be transported to the outside. vesicular organelles of the cell, such as the sarcoplasmic Therefore, the sodium ion binds to the carrier protein where it reticulum of muscle cells and the mitochondria in all cells. projects to the exterior surface of the membrane, while the substance to be counter-transported binds to the interior projection of the carrier protein. Once both have become bound, Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 a conformational change occurs, and energy released by the action of the sodium ion moving to the interior causes the other Mechanism for transport of a substance through cellular sheet: substance to move to the exterior. 1. Active transport through the cell membrane on one side of the Examples of Secondary Active Transport transporting cells in the sheet, 2. Either simple diffusion or facilitated diffusion through the 1. Co-Transport of Glucose and Amino Acids Along with membrane on the opposite side of the cell. Sodium Ions Other Type of Active Transport Sodium co-transport of Glucose- that the transport carrier protein has two binding sites on its exterior side, one for Vesicular sodium and one for glucose. Also, the concentration of sodium ions is high on the outside and low inside, which Endocytosis - into the cell provides energy for the transport. A special property of the Exocytosis- exiting the cell transport protein is that a conformational change to allow sodium movement to the interior will not occur until glucose MEMBRANE POTENTIAL molecule also attaches. When they both become attached, the conformational change takes place, and the sodium and Approximate concentration of important electrolytes and glucose are transported to the inside of the cell at the same other substances in the ECF and ICF. time. 1. Note that the ECF contains large amount of Na+, Sodium co-transport of Amino acids -occurs in the same but small amount of K+. The opposite is true of the manner as for glucose, except that it uses a different set of ICF. The ECF contains large amount of Cl- ions transport proteins. At least five amino acid transport proteins where the ICF contains very little of these ions. have been identified, each of which is responsible for 2. Predominant ions outside the cell: Na+, Ca+, transporting one subset of amino acids with specific HCO3-, Cl-, Glucose molecular characteristics. 3. Predominant ions inside the cell: K+, Mg+, PO4, negatively charge anions (amino acid/proteins) 2. Sodium Counter-Transport of Calcium and Hydrogen Resting membrane potential of large fibers when they are not Ions transmitting nerve signals is above -90 millivolts. That is the potential inside the fiber. Sodium-calcium counter-transport- occurs through all or almost all cell membranes, with sodium ions moving to the Factors that determine the level of the resting membrane interior and calcium ions to the exterior; both are bound to potential: the same transport protein in a counter-transport mode. This 1. All cellular base of the body have a powerful Na+-K+ mechanism is in addition to primary active transport of pump. calcium that occurs in some cells. ▪ Na+-K+ pump continually transport Na+ ions to the Sodium-hydrogen counter-transport- occurs in several outside, and K+ ions to the inside of the cell. Note tissues. An especially important example is in the proximal that this is an electrogenic pump (would cause a tubules of the kidneys, where sodium ions move from the negative charge inside the membrane) lumen of the tubule to the interior of the tubular cell while ▪ There is a net deficit of positive ions on the inside hydrogen ions are counter-transported into the tubule lumen. causing a negative potential inside the cell As a mechanism for concentrating hydrogen ions, counter- membrane. transport is not nearly as powerful as the primary active ▪ The one that caused a negative potential inside is transport of hydrogen ions that occurs in the more distal the Na+-K+ pump. renal tubules, but it can transport extremely large numbers ▪ The Na+-K+ pump also causes a large of hydrogen ions, thus making it a key to hydrogen ion concentration gradient for Na+ and K+ across the control in the body fluids resting membrane potential. 2. Channel protein ACTIVE TRANSPORT THROUGH CELLULAR SHEETS ▪ Sometimes called tandem pore domain, potassium channel, potassium (K+) “leak” channel, or IRC (inward rectifying channel) At many places in the body, substances must be transported all the ▪ Good channel for K+ to pass outside the cell way through a cellular sheet instead of simply through the cell ▪ This potassium leak channel may also leak Na+ ions membrane. slightly, but are far more permeable to K+ than to Na+ Transport occurs through the: – normally about 100 times as permeable. 1. Intestinal epithelium, ▪ This differential in permeability is a key factor in 2. Epithelium of the renal tubules, determining the level of the normal resting membrane 3. Epithelium of all exocrine glands, potential 4. Epithelium of the gallbladder 5. Membrane of the choroid plexus of the brain along with other When the Membrane Is Permeable to Several Different Ions the membranes. diffusion potential that develops depends on three factors: a. the polarity of the electrical charge of each ion b. the permeability of the membrane to each ion c. the concentrations of the respective ions on the inside and outside of the membrane Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 Goldman equation or the Goldman-Hodgkin-Katz equation ACTION POTENTIALS Is used to calculate membrane potential on the inside of the membrane when two univalent positive ions, sodium (Na+) and potassium (K+), Are rapid changes in the membrane potential that spread rapidly and one univalent negative ion, chloride (Cl−), are involved. along the nerve fiber membrane. Each action potential begins with a sudden change from the normal resting negative membrane potential to a positive potential and ends with an almost equally rapid change How did they arrive at -90mV as the resting membrane potential? back to the negative potential. To conduct a nerve signal, the action potential moves along the nerve fiber until it comes to the fiber’s end. The successive stages of the action potential: Derived from the Nernst potential of K, which is -94mV and the 1. Resting Stage. The resting stage is the resting membrane Nernst potential of Na which is +61 mV. potential before the action potential begins. The membrane is Used Goldman equation -> calculates the membrane potential said to be “polarized” during this stage because of the −90 on the inside of the membrane when Na+, K+, Cl- are involved millivolts negative membrane potential that is present. Diffusion potentials alone caused by K+ and Na+ diffusion would give membrane potential of about -86 millivolts, with almost all 2. Depolarization Stage- the membrane suddenly becomes of this being determined by K+ diffusion. permeable to sodium ions, allowing tremendous numbers of The continuous pumping of 3 Na+ ions to the inside occurs for positively charged sodium ions to diffuse to the interior of the each 2 K+ ions being pumped to the inside of the membrane axon. Depolarization- The normal “polarized” state of −90 millivolts The pumping of more Na+ ions to the outside than the K+ ions is immediately neutralized by the inflowing positively being pumped to the inside causes continual loss of positive charged sodium ions, with the potential rising rapidly in the charges from inside the membrane, creating an additional positive direction. degree of negativity on the inside beyond that which can be accounted for by diffusion alone In large nerve fibers, the great excess of positive sodium Additional -4 millivolts is contributed to the membrane potential ions moving to the inside causes the membrane potential to by the continuously acting electrogenic Na+-K+ pump giving a actually “overshoot” beyond the zero level and to become net membrane potential of -90 mV. somewhat positive. In some smaller fibers, as well as in many central nervous system neurons, the potential merely approaches the zero level and does not overshoot to the positive state. 3. Repolarization Stage- Happens within a few 10,000ths of a sec- ond after the membrane becomes highly permeable to sodium ions, the sodium channels begin to close and the potassium channels open to a greater degree than normal. Repolarization of the membrane- rapid diffusion of potassium ions to the exterior re-establishes the normal negative resting membrane potential, which is called. Figure 7: Typical action potential recorded Figure 6. Establishment of resting membrane potentials in nerve fibers Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 VOLTAGE-GATED SODIUM AND POTASSIUM CHANNELS During the resting state, the gate of the potassium channel is closed and potassium ions are prevented from passing through this channel Voltage-Gated Sodium Channel-The necessary actor in causing to the exterior. both depolarization and repolarization of the nerve membrane during the action potential is the How will the voltage gated potassium channel speed up the repolarization? Voltage-Gated Potassium Channel- plays an important role in increasing the rapidity of repolarization of the membrane. Answer: When the membrane potential rises from −90 millivolts toward zero, this voltage change causes a conformational opening of the gate and allows increased potassium diffusion outward through the channel. *These two voltage-gated channels are in addition to the The decreases in sodium entry to the cell and the simultaneous Na+-K+ pump and the K+ leak channels that works in increase in potassium exit from the cell combine to speed the Resting Membrane Potential repolarization process, leading to full recovery of the resting *In Action Potential the ones that are work are the Voltage- membrane potential within another few 10,000ths of a second. Gated Sodium-Potassium Channels ACTION POTENTIAL A. Summarized events that cause action potential. QUESTIONS FROM THE LECTURE 1. During the resting state, before the action potential begins, the conductance for potassium ions is 50 to 100 times as great as the During the resting stage what is state of the activation gate of the conductance for sodium ions. This disparity is caused by much voltage gated sodium channels? greater leakage of potassium ions than sodium ions through the leak channels. Answer: 2. At the onset of the action potential, the sodium channels The activation gate is closed, which prevents any entry of sodium ions instantaneously become activated and allow up to a 5000-fold to the interior of the fiber through these sodium channels. increase in sodium conductance. The inactivation process then closes the sodium channels within another fraction of a milli- What Millivolts will these gates Open? second. The onset of the action potential also causes voltage gating of the potassium channels, causing them to begin opening Answer: more slowly a fraction of a millisecond after the sodium channels open. −70 and −50 millivolts—that causes a sudden conformational change 3. At the end of the action potential, the return of the membrane in the activation gate, flipping it all the way to the open position. potential to the negative state causes the potassium channels to What happened to the inactivation of the voltage gated sodium close back to their original status, but again, only after an channel during repolarization? additional millisecond or more delay. Answer: During the early portion of the action potential, the ratio of sodium to potassium conductance increases more than 1000-fold. Therefore, far The inactivation gate, however, closes a few 10,000ths of a second more sodium ions flow to the interior of the fiber than do potassium after the activation gate opens. That is, the conformational change that ions to the exterior. This is what causes the membrane potential to flips the inactivation gate to the closed state is a slower process than become positive at the action potential onset. Then the sodium the conformational change that opens the activation gate. Therefore, channels begin to close and the potassium channels begin to open, after the sodium channel has remained open for a few 10,000ths of a and thus the ratio of conductance shifts far in favor of high potassium second, the inactivation gate closes and sodium ions no longer can conductance but low sodium conductance. This shift allows very rapid pour to the inside of the membrane. At this point, the membrane loss of potassium ions to the exterior but virtually zero flow of sodium potential begins to return toward the resting membrane state ions to the interior. Consequently, the action potential quickly returns (Repolarization) to its baseline level. When the membrane potential is near the resting membrane B. Roles of Other Ions During the Action Potential potential what will happen to inactivation gates? At least two other types of ions must be considered: Answer: Negative anions Calcium ions The inactivation gate will not reopen until the membrane potential returns to or near the original resting membrane potential leve 1. Impermeant Negatively Charged Ions (Anions) Inside the Nerve Axon -Inside the axon are many negatively charged During the resting stage what is the state of voltage gated ions that cannot go through the membrane channels. They potassium channel? include the anions of protein molecules and of many organic phosphate compounds, sulfate compounds, and so forth. Answer: Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 These ions cannot leave the interior of the axon, any deficit of An excitable membrane has no single direction of propagation, but positive ions inside the membrane leaves an excess of these the action potential travels in all directions away from the impermeant negative anions. Therefore, these impermeant stimulus—even along all branches of a nerve fiber—until the entire negative ions are responsible for the negative charge inside the membrane has become depolarized. fiber when there is a net deficit of positively charged potassium ions and other positive ions. All-or-Nothing Principle Once an action potential has been elicited at any point on the 2. Calcium Ions. The membranes of almost all cells of the body membrane of a normal fiber, the depolarization process travels have a calcium pump similar to the sodium pump, and calcium over the entire membrane if conditions are right, but it does not serves along with (or instead of) sodium in some cells to travel at all if conditions are not rightt. It also applies to all normal cause most of the action potential. Calcium pump transports excitable tissues. calcium ions from the interior to the exterior of the cell Occasionally, the action potential reaches a point on the membrane (or into the endoplasmic reticulum of the cell). membrane at which it does not generate sufficient voltage to stimulate the next area of the membrane. When this situation A major function of the voltage-gated calcium ion channels is to occurs, the spread of depolarization stops. contribute to the depolarizing phase on the action potential in some cells, especially in both cardiac muscle and smooth muscle. Safety factor for propagation Calcium channels are slow channels (Slow gating) and Sodium For continued propagation of an impulse to occur, the ratio of channels are fast channels (Fast Gating) action potential to threshold for excitation must at all times be greater than 1 Another importance is of Calcium channels is the Increased Permeability of the Sodium Channels When There Is a Deficit of Calcium Ions (hypocalcemia) the sodium channels become activated (increased permeability) by a small increase of the membrane potential from its normal, very negative level. The nerve fiber becomes highly excitable, sometimes discharging repetitively without provocation rather than remaining in the resting state. When there is spontaneous discharge that occurs in some peripheral nerves, it will cause muscle “tetany “or continuous muscle contraction or muscle spasm. A. INITIATION OF THE ACTION POTENTIAL Positive-Feedback Cycle -First, as long as the membrane of the nerve fiber remains undisturbed, no action potential occurs in the normal nerve. If any event causes enough initial rise in the membrane potential from −90 millivolts toward the zero level, the rising voltage will cause many voltage-gated sodium Figure 7. Propagation of action potentials in both directions along a channels to begin opening. This occurrence allows rapid conductive fiber. inflow of sodium ions, which causes a further rise in the membrane potential, thus opening still more voltage-gated sodium channels and allowing more streaming of sodium. ions to the interior of the fiber. Once the feedback is strong enough, continues until all the voltage-gated sodium channels have become activated (opened). Then, within another fraction of a millisecond, the rising membrane potential causes closure of the sodium chan- nels and opening of potassium channels, and the action potential soon terminates. Threshold for Initiation of the Action Potential This level of −65 millivolts and is said to be the threshold for stimulation. B. PROPAGATION OF THE ACTION POTENTIAL An action potential elicited at any one point on an excitable membrane usually excites adjacent portions of the membrane, resulting in propagation of the action potential along the membrane. Direction of Propagation Prepared and Edited By: Group 8  (002) TRANSPORT OF SUBSTANCES THROUGH CELL MEMBRANES AND MEMBRANE POTENTIALS AND ACTION POTENTIALS DR. CARINGAL | 10/07/2020 APPENDIX ISOSMOTIC VS ISOTONIC Osmolarity is not the same as tonicity. Both terms describe solutions, but the similarity ends there. Tonicity is a behaviorall term. It describes what a solution would do to a cell's volume at equilibrium if the cell was placed in the solution. It tells what effect a solution has on a cell, and it depends both on the osmolarity of the solution and on whether or not solutes in the solution can enter the cell Cannot be measured on an osmometer, and it has no units. Importance of the about the difference between osmolarity and tonicity - Understanding tonicity is the basis for intravenous (iv) fluid therapy, and administering the wrong iv solution to patients can harm or even kill them. Unfortunately, many easily accessed resources attempting to explain osmolarity and tonicity are either wrong or so vague that they create misunderstanding. Isotonic solution: a solution that has the same salt concentration (0.85 -0.9%) as cells and blood When two environments are isotonic, the total molar concentration of dissolved solutes is the same in both of them Example Osmolarity and tonicity of two of the most commonly used iv solutions: normal saline (or 0.9% NaCl) and D-5-W [or 5% dextrose (glucose)] in water. If we measure their concentrations on an osmometer, we find that they are both 278 mOsmol/l, so they are isosmotic. But if we administer them to a person by an iv infusion, we find that normal saline is isotonic because NaCl does not enter cells, whereas D-5-W is hypotonic because glucose goes into cells. Here is an important example of when isosmotic is not isotonic. Remember blood glucose homeostasis. If you give someone an iv of glucose solution, such as D-5-W, over time all of the glucose you gave them will go into cells. As glucose enters cells, the movement of solute from the extracellular fluid into the cells causes water to follow by osmosis. The cell gains volume, so the solution is hypotonic. Glucose inside the cell is metabolized by aerobic respiration with the end products of CO2 and water. So the end result of giving a D-5-W solution is the same as if you gave the person pure water. The bottom line: isosmotic solutions are not always isotonic. Hyperosmotic solutions are not always hypertonic. But hypoosmotic solutions are always hypotonic. Reference: https://journals.physiology.org/doi/full/10.1152/advan.00080.20 16 Prepared and Edited By: Group 8