Action Potential PDF

Action potentials Physiology lecture 2 DR. WAFA ALSHAIBY [email protected] BASIC PHYSICS OF MEMBRANE POTENTIALS Membrane Potentials Caused by Ion Concentration Differences Across a Selectively Permeable Membrane. the potassium concentration is great inside a nerve fiber membrane but ve...

Action potentials Physiology lecture 2 DR. WAFA ALSHAIBY [email protected] BASIC PHYSICS OF MEMBRANE POTENTIALS Membrane Potentials Caused by Ion Concentration Differences Across a Selectively Permeable Membrane. the potassium concentration is great inside a nerve fiber membrane but very low outside the membrane. Let us assume that the membrane in this case is permeable to the potassium ions but not to any other ions. Because of the large potassium concentration gradient from the inside toward the outside, there is a strong tendency for potassium ions to diffuse outward through the membrane. As they do so, they carry positive electrical charges to the outside, thus creating electropositivity outside the membrane and electronegativity inside the membrane because of negative anions that remain behind and do not diffuse outward with the potassium. Within about 1 millisecond, the potential difference between the inside and outside, called the diffusion potential, becomes great enough to block further net potassium diffusion to the exterior, despite the high potassium ion concentration gradient. In the normal mammalian nerve fiber, the potential difference is about 94 millivolts, with negativity inside the fiber membrane. this time with a high concentration of sodium ions outside the membrane and a low concentration of sodium ions inside. These ions are also positively charged. This time, the membrane is highly permeable to the sodium ions but is impermeable to all other ions. Diffusion of the positively charged sodium ions to the inside creates a membrane potential of opposite polarity to that in Figure 5-1A,with negativity outside and positivity inside. Again, the membrane potential rises high enough within milliseconds to block further net diffusion of sodium ions to the inside; however, this time, in the mammalian nerve fiber, the potential is about 61 millivolts positive inside the fiber. Thus, in both parts of Figure 5-1, we see that a concentration difference of ions across a selectively permeable membrane can, under appropriate conditions, createa membrane potential. Later in this chapter, we show that many of the rapid changes in membrane potentials observed during nerve and muscle impulse transmission result from such rapidly changing diffusion potentials. The G oldman Equation Is Used to Calculate the Diffusion Potential When the Membrane Is Permeable to Several Different Ions. When a membrane is permeable to several different ions, the diffusion potential that develops depends on three factors: (1) the polarity of the electrical charge of each ion; (2) the permeability of the membrane (P) to each ion; and (3) the concentration (C) of the respective ions on the inside (i) and outside (o) of the membrane. Thus, the following formula, called the Goldman equation or the Goldman-Hodgkin-Katz equation, gives the calculated membrane potential on the inside of the membrane when two univalent positive ions, sodium (Na+) and potassium (K+), and one univalent negative ion, chloride (Cl−), are involved. Several key points become evident from the Goldman equation. First, sodium, potassium, and chloride ions are the most important ions involved in the development of membrane potentials in nerve and muscle fibers, as well as in the neuronal cells. The concentration gradient of each of these ions across the membrane helps determine the voltage of the membrane potential. Second, the quantitative importance of each of the ions in determining the voltage is proportional to the membrane permeability for that particular ion. If the membrane has zero permeability to sodium and chloride ions, the membrane potential becomes entirely dominated by the concentration gradient of potassium ions alone, and the resulting potential will be equal to the Nernst potential for potassium. The same holds true for each of the other two ions if the membrane should become selectively permeable for either one of them alone. Third, a positive ion concentration gradient from inside the membrane to the outside causes electronegativity inside the membrane. The reason for this phenomenon is that excess positive ions diffuse to the outside when their concentration is higher inside than outside the membrane. This diffusion carries positive charges to the outside but leaves the non diffusible negative anions on the inside, thus creating electronegativity on the inside. The opposite effect occurs when there is a gradient for a negative ion. That is, a chloride ion gradient from the outside to the inside causes negativity inside the cell because excess negatively charged chloride ions diffuse to the inside while leaving the nondiffusible positive ions on the outside. Fourth, as explained later, the permeability of the sodium and potassium channels undergoes rapid changes during transmission of a nerve impulse, whereas the permeability of the chloride channels does not change greatly during this process. Therefore, rapid changes in sodium and potassium permeability are primarily responsible for signal transmission in neurons. Resting Membrane Potential of Different Cell Types. In some cells, such as the cardiac pacemaker cells, the membrane potential is continuously changing, and the cells are never “resting”. In many other cells, even excitable cells, there is a quiescent period in which a resting membrane potential can be measured. Table 5-1 shows the approximate resting membrane potentials of some different types of cells. The membrane potential is obviously very dynamic in excitable cells such as neurons, in which action potentials occur. However, even in nonexcitable cells, the membrane potential (voltage) also changes in response to various stimuli, which alter activities for the various ion transporters, ion channels, and membrane permeability for sodium, potassium, calcium, and chloride ions. The resting membrane potential is, therefore, only a brief transient state for many cells. Electrochemical Driving Force. When multiple ions contribute to the membrane potential, the equilibrium potential for any of the contributing ions will differ from the membrane potential. NEURON ACTION POTENTIAL Nerve signals are transmitted by action potentials, which are rapid changes in the membrane potential that spread rapidly 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 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., with the transfer of positive charges to the interior of the fiber at its onset and the return of positive charges to the exterior at its end. successive changes in membrane potential over a few 10,000ths of a second, illustrating the explosive onset of the action potential and the almost equally rapid recovery. The successive stages of the action potential are as follows. Resting Stage. The resting stage is the resting membrane potential before the action potential begins. The membrane is said to be “polarized” during this stage becauseof the −70 millivolts negative Membrane Potential that is present. Depolarization Stage. At this time, the membrane suddenly becomes permeable to sodium ions, allowing rapid diffusion of positively charged sodium ions to the interior of the axon. The normal polarized state of −70 millivolts is immediately neutralized by the inflowing, positively charged sodium ions, with the potential rising rapidly in the positive direction—a process called depolarization. In large nerve fibers, the great excess of positive sodium ions moving to the inside causes the membrane potential to actually overshoot beyond the zero level and to become somewhat positive. In some smaller fibers, as wellas in many central nervous system neurons, the potential merely approaches the zero level and does not overshoot to the positive state.... Repolarization Stage. Within a few 10,000ths of a second 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. Then, rapid diffusion of potassium ions to the exterior re-establishes the normal negative resting membrane potential, which is called repolarization of the membrane. To explain more fully the factors that cause both depolarization and repolarization, we will describe the special characteristics of two other types of transport channels through the nerve membrane, the voltage-gated Sodium and potassium channels. VOLTAG E-G ATED SODIU M AND POTASSIU M CHANNELS The necessary factor in causing both depolarization and repolarization of the nerve membrane during the action potential is the voltage-gated sodium channel. A voltage-gated potassium channel also plays an important role in increasing the rapidity of repolarization of the membrane. These two voltage-gated channels are in addition to the Na+-K+ pump and the K+ leak channels. SU MMARY OF EVENTS THAT CAU SE THE ACTION POTENTIAL Figure 5-10 summarizes the sequential events that occur during and shortly after the action potential. The bottom of the figure shows the changes in membrane conductance for sodium and potassium ions. During the resting state, before the action potential begins, the conductance for potassium ions is 50 to 100 times as great as the conductance for sodium ions. This disparity is caused by much greater leakage of potassium ions than sodium ions through the leak channels. However, at the onset of the action potential, the sodium channels almost instantaneously become activated and allow up to a 5000-fold increase in sodium conductance. The inactivation process then closes the sodium channels within another fraction of a millisecond. The onset of the action potential also initiates voltage gating of the potassium channels, causing them to begin opening more slowly, a fraction of a millisecond after the sodium channels open. At the end of the action potential, the return of the membrane potential to the negative state causes the potassium channels to close back to their original status but, again, only after an additional millisecond or more delay. The middle portion of Figure 5-10 shows the ratio of sodium to potassium conductance at each instant during the action potential, and above this depiction is the action potential itself. During the early portion of the action potential, the ratio of sodium to potassium conductance increases more than 1000 -fold.Therefore, far more sodium ions flow to the interior of the fiber than potassium ions to the exterior. This is what causes the membrane potential to become positive at the action potential onset. Then, the sodium channels begin to close, and the potassium channels begin to open; thus, the ratio of conductance shifts far in favor of high potassium conductance but low sodium conductance. This shift allows for a very rapid loss of potassium ions to the exterior but virtually zero flow of sodium ions to the interior. Consequently, the action potential quickly returns to its baseline level Roles of Other Ions During the Action Potential Calcium Ions. The membranes of almost all cells of the body have a calcium pump similar to the sodium pump, and calcium serves along with (or instead of) sodium in some cells to cause most of the action potential. Like the sodium pump, the calcium pump transports calcium ions from the interior to the exterior of the cell membrane (or into the endoplasmic reticulum of the cell), creating a calcium ion gradient of about 10,000-fold.This process leaves an internal cell concentration of calcium ions of about 10−7 molar, in contrast to an external concentration of about10−3 molar. In addition, there are voltage-gated calcium channels. Because the calcium ion concentration is more than 10,000 times greater in the extracellular fluid than in the intracellularfluid, there is a tremendous diffusion gradient and elec-trochemical driving force for the passive flow of calcium ions into the cells. These channels are slightly permeable to sodium ions and calcium ions, but their permeability to calcium is about 1000-foldgreater than to sodium under normal physiological conditions.  SKELETAL MUSCLE CONTRACTION AND RELAXATION. The sequence of events that result in the contraction of an individual muscle fiber begins with a signal—the neurotransmitter, ACh—from the motor neuron innervating that fiber. The local membrane of the fiber will depolarize as positively charged sodium ions (Na+) enter, triggering an action potential that spreads to the rest of the membrane will depolarize, including the T-tubules. This triggers the release of calcium ions (Ca++) from storage in the sarcoplasmic reticulum (SR). The Ca++ then initiates contraction, which is sustained by ATP. As long as Ca++ ions remain in the sarcoplasm to bind to troponin, which keeps the actin-binding sites “unshielded,” and as long as ATP is available to drive the cross-bridge cycling and the pulling of actin strands by myosin, the muscle fiber will continue to shorten to an anatomical limit. MUSCLE CONTRACTION SKELETAL MUSCLE CONTRACTION AND RELAXATION (STRIATED MUSCLE). Muscle contraction usually stops when signaling from the motor neuron ends, which repolarizes the sarcolemma and T-tubules, and closes the voltage-gated calcium channels in the SR. Ca++ ions are then pumped back into the SR, which causes the tropomyosin to reshield (or re-cover) the binding sites on the actin strands. A muscle also can stop contracting when it runs out of ATP and becomes fatigued MUSCLE RELAXATION  SMOOTH MUSCLE CONTRACTION AND RELAXATION smooth muscle cells do not contain troponin, cross-bridge formation is not regulated by the troponin-tropomyosin complex but instead by the regulatory protein calmodulin. In a smooth muscle fiber, external Ca++ ions passing through opened calcium channels in the sarcolemma, and additional Ca++ released from SR, bind to calmodulin. The Ca++-calmodulin complex then activates an enzyme called myosin (light chain) kinase, which, in turn, activates the myosin heads by phosphorylating them (converting ATP to ADP and Pi, with the Pi attaching to the head). The heads can then attach to actin-binding sites and pull on the thin filaments. The thin filaments also are anchored to the dense bodies; the structures invested in the inner membrane of the sarcolemma (at adherens junctions) that also have cord-like intermediate filaments attached to them. When the thin filaments slide past the thick filaments, they pull on the dense bodies, structures tethered to the sarcolemma, which then pull on the intermediate filaments networks throughout the sarcoplasm. This arrangement causes the entire muscle fiber to contract in a manner whereby the ends are pulled toward the center, causing the midsection to bulge in a corkscrew motion. Muscle contraction continues until ATP-dependent calcium pumps actively transport Ca++ ions back into the SR and out of the cell. However, a low concentration of calcium remains in the sarcoplasm to maintain muscle tone. This remaining calcium keeps the muscle slightly contracted, which is important in certain tracts and around blood vessels. Although smooth muscle contraction relies on the presence of Ca++ ions, smooth muscle fibers have a much smaller diameter than skeletal muscle cells. T-tubules are not required to reach the interior of the cell and therefore not necessary to transmit an action potential deep into the fiber. Smooth muscle fibers have a limited calcium-storing SR but have calcium channels in the sarcolemma (similar to cardiac muscle fibers) that open during the action potential along the sarcolemma. The influx of extracellular Ca++ ions, which diffuse into the sarcoplasm to reach the calmodulin, accounts for most of the Ca++ that triggers contraction of a smooth muscle cell.