Membrane Potential and Action Potential.pdf

Membrane Potential Action potential and Electrical Neurotransmission Afnan Atallah, Ph.D. Al-Quds University  Resting Membrane Potential Potassium (K+) is the major cation within cells and sodium (Na+) dominates the extracellular fluid Chloride ions (Cl-) mos...

Membrane Potential Action potential and Electrical Neurotransmission Afnan Atallah, Ph.D. Al-Quds University  Resting Membrane Potential Potassium (K+) is the major cation within cells and sodium (Na+) dominates the extracellular fluid Chloride ions (Cl-) mostly remain with Na+ in the extracellular fluid. Phosphate ions and negatively charged proteins are the major anions of the intracellular fluid.  Resting Membrane Potential The intracellular compartment contains some anions that do not have matching cations, giving the cells a net negative charge. The extracellular compartment has the cations, giving the ECF a net positive charge. One consequence of this uneven distribution of ions is that the intracellular and extracellular compartments are not in electrical equilibrium.  Membrane potential The electrical disequilibrium that exists between ECF and ICF of living cells is called the membrane potential difference (Vm), or membrane potential The membrane potential results from the uneven distribution of electrical charge (i.e., ions) between the ECF and ICF.  Membrane potential  To show how a membrane potential difference can arise from ion concentration gradients and a selectively permeable membrane, we will use an artificial cell system where we can control the membrane’s permeability to ions and the composition of the ECF and ICF.  At equilibrium state, cells and solution are electrically and chemically equal. What creates membrane potential? 1. Ion concentration gradients between the ECF and ICF 2. The selectively permeable cell membrane  Membrane potential At disequilibrium, cells and solution are electrically and chemically imbalance.  Active transport carrier protein is inserted into the membrane Energy is need to pump one cation out of the cell  net charge of -1 inside the cell and +1 outside the cell. The input of energy to transport ions across the membrane has created an electrical gradient.  The Resting Membrane Potential An electrical gradient between ECF and ICF is known as the Resting Membrane Potential difference (Vm).  Membrane potential  The Resting Membrane Potential Is Due Mostly to Potassium.  The equilibrium potential (Eion) for any ion at 37° C (human body temperature) can be calculated using the Nernst equation: Where 61 is 2.303 RT/F at 37° C* z is the electrical charge on the ion ( 1 for K ) [ion]out and [ion]in are the ion concentrations outside and inside the cell. Eion is measured in mV.  Membrane potential  Concentration gradient for K is 150mM inside and 5mM outside the cell  The equilibrium potential for potassium (EK) is -90 mV  Membrane potential  The concentration gradient moving Na+ into the cell (150 mM outside, 15 mM inside)  The equilibrium potential for Sodium (ENa) is + 60 mV  Membrane potential  In reality, living cells are not permeable to only one ion  If a cell is permeable to several ions, we cannot use the Nernst equation to calculate membrane potential. Instead we must use a related equation called the Goldman equation  In fact, living cells are not permeable to only one ion Goldman Equation Pk[Ko] + PNa[Nao] Vm = 60 log10 Pk[Kin] + PNa[Nain] = -70 mV  The GHK Equation Predicts Membrane Potential Using Multiple Ions The Goldman-Hodgkin-Katz (GHK) equation calculates the membrane potential that results from the contribution of all ions that can cross the membrane. The GHK equation includes membrane permeability values If the membrane is not permeable to a particular ion, that ion does not affect the membrane potential. For mammalian cells, we assume that Na+, K+, and Cl- are the three ions that influence membrane potential in resting cells.  Membrane potential  Cell has a resting membrane potential of -70 mV.  Most cells are about 40 times more permeable to K than to Na.  As a result, a cell resting membrane potential is closer to the EK of -90 mV than to the ENa of +60 mV.  Na+ and K+ that leaks is promptly pumped back by the Na – K ATPase  helps maintain the electrical gradient.  Membrane potential  The membrane potential (Vm) begins at a steady resting value of -70 mV  When the trace moves upward (becomes less negative) the cell is said to have depolarized.  A return to the resting membrane potential is termed repolarization.  If the resting potential (becomes more negative) the potential difference has increased, and the cell has hyperpolarized.  Ion movement creates electrical signals  Electrical Signals: Action Potential An action potential: is a rapid sequence of changes in the voltage across a membrane. It is a short – lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Occur in several types of animal cells, called excitable cells, which include (neurons, muscle cells, and endocrine cells). Is generated by special types of voltage-gated ion channels embedded in a cell's plasma membrane.  These channels are shut when the membrane potential is near the resting potential of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold.  Action Potential The action potential has five phases: 1. Reaching threshold. 2. Depolarization. 3. Repolarization. 4. Hyperpolarization. 5. Return to resting potential.  Action Potential Threshold: a certain minimum strength required to stimulate an axon in order to generate action potential. All or none: each action potential has the same amplitude independently from the strength of the stimulus. Refractory period: a second action potential cannot occur during this period. HOW ACTION POTENTIAL HAPPENS? Action Potential  Action Potential Cell is more positive outside than inside.  Action Potential As ions move across the membrane the potential increases.  Action Potential  Level of depolarization needed to trigger an action potential (most neurons have a threshold at -50 mV)  Threshold reflects the need to trigger the opening of the voltage-gated sodium channel (need a depolarization of about 10 to 15 mV to open)  Action Potential Action potential rising phase  As sodium channels open, Na+ ions flow into cell, depolarizes the cell more and more sodium channels open = drives the membrane potential towards a peak of the Nernst equilibrium potential for Na+  Action Potential  During an action potential the membrane potential goes towards the Nernst equilibrium potential for Na+.  In terms of Goldman-Katz equation now permeability to Na+ is dominant (K+ and Cl- minor components) therefore membrane potential goes towards ENa.  Action Potential K+ moves out of the cell along its gradient and the inside of the cell becomes more and more negative.  Action Potential Falling Phase of Action Potential After reaches peak now action potential falls, membrane potential falls back towards rest. Why doesn't the action potential stay around ENa? Two reasons: I. Na+ channels move into an inactive state (close) II. Delayed K+ channels open  Action Potential Inactivating Na+ channels. Na+ channels go to an inactivated state after 1-2 msec. after first opening. When Inactivated can not be reopened. Therefore the membrane potential now determined mostly by K+ (same as for resting potential) and membrane starts to repolarize.  Action Potential Delayed K+ channels open (called delayed rectifier; voltage-gated like Na+ channel) Open after about 1-2 msec of threshold depolarization. Now K+ flows out of the cell and speeds the repolarization process. Cause the hyperpolarization because open K+ channels make the K+ permeability higher than at rest and membrane more negative on inside. Hyperpolarization of membrane causes K+ channels to close. Membrane settles back to rest.  Action Potential Hyperpolarization occurs when the membrane potential drops below resting potential; caused by the continuing movement of K+ out of the cell.  Action Potential  Repolarization: Voltage-gated Na+ channels and voltage-gated K+ channels now closed so the membrane goes back to the resting state i.e. the leak channels are the only channels open and again set the membrane potential.  Action Potential Returns to its original state where the outside is more positive than the inside and the membrane potential is -70 mv.  Action Potential  A second action potential cannot be triggered for about 2 msec, no matter how large the stimulus.  This 2 msec represents the time required for the Na+ channel gates to reset to their resting positions and is called the absolute refractory period  Relative refractory period follows the absolute refractory period.  During the relative refractory period, some but not all Na+ channel gates have reset to their original positions. Those channels can be opened by a higher-than-normal graded potential  This means that a stronger-than-normal depolarizing graded potential is needed to bring the cell up to threshold  During the relative refractory period, K+ channels are still open Ion Movement During an Action Potential  Neurons: Cellular and Network Properties Action Potentials Action potentials are very brief, large depolarizations that travel for long distances through a neuron without losing strength. Their function is rapid signalling over long distances.  Graded Potentials Graded Potentials reflect stimulus strength. The wave of depolarization that moves through the cell is known as local current flow.  Graded Potentials The cell body receives stimulus. The strength is determined by how much charge enters the cell. The strength of the graded potential diminishes over distance due to current leak and cytoplasmic resistance. The amplitude increases as more sodium enters, the higher the amplitude, the further the spread of the signal.  Graded Potentials Subthreshold and suprathreshold graded potentials in a neuron. If a graded potential does not go beyond the threshold at the trigger zone an action potential will not be generated.  Graded Potentials  Why do graded potentials lose strength as they move through the cytoplasm?  There are two reasons: I. Current leak: Some of the positive ions leak back across the membrane as the depolarization wave moves through the cell. The membrane in the neuron cell body is not a good insulator and has open leak channels that allow positive charge to flow out into the ECF. II. Cytoplasmic resistance: The cytoplasm itself provides resistance to the flow of electricity, just as water creates resistance that diminishes the waves from the stone. Graded Potential vs Action Potential  Graded Potentials  Depolarizing grading potential are excitatory.  Hyperpolarizing graded potentials are inhibitory.  Graded potential:  Short distance.  Lose strength as they travel.  Can initiate an action potential.  Electrical Signals: Trigger Zone Graded potential enters trigger zone, summation brings it to a level above threshold. Voltage-gated Na+ channels open and Na+ enters axon, a segment of the membrane depolarizes. Positive charge spreads along adjacent sections of axon by local current flow, as the signal moves away the currently stimulated area returns to its resting potential. Local current flow causes new section of the membrane to depolarize, this new section is creating a new set of action potentials that will trigger the next area to be depolarized. The refractory period prevents backward conduction; loss of K+ repolarizes the membrane, Once the Na+ close they will not open in response to backward conduction until they have reset to their resting position- ensures only one action potential is initiated at time.  Frequency of Action Potentials  The frequency of action potential firing indicates the strength of a stimulus.  "Wave" of Aps.  Proportional Neurotransmitter (NT) Release.  Stronger GP Initiates more APs & more NT.  A GP reaching the trigger zone does not usually trigger a single AP.  Instead, even a small GP that is above threshold triggers a burst of AP.  Frequency of Action Potentials  The amount of neurotransmitter released at the axon terminal is directly related to the total number of action potentials that arrive at the terminal per unit time.  Frequency of Action Potentials  Stronger stimuli release more neurotransmitter into the synapse.  Conduction of Action Potentials  The wave of depolarization that moves through the cell is known as local current flow.  The net movement of positive electrical charge. Conduction of Action Potentials Conduction of Action Potentials Conduction of Action Potentials Conduction of Action Potentials  Conduction of Action Potentials  Because of the absolute refractory period, a second action potential cannot occur before the first has finished.  Action potentials moving from trigger zone to axon terminal cannot overlap and cannot travel backward.  Conduction of Action Potentials  Depolarization makes a neuron more likely to fire an action potential, depolarizing graded potentials are considered to be Excitatory. (involve Na channel)  Hyperpolarizing graded potential moves the membrane potential farther from the threshold value and makes the neuron less likely to fire an action potential. hyperpolarizing graded potentials are considered to be Inhibitory. (involve Cl channel)  Conduction of Action Potentials Larger Diameter Faster Conduction Myelinated Axon Faster Conduction Will be discussed Salutatory Conduction in the next topic Disease Damage to Myelin Chemicals that Block Channels Alteration of ECF Ion Concentrations  Alteration of ECF Ion Concentrations  When blood K is in the normal range (normokalemia)  A subthreshold graded potential does not fire an action potential.  A suprathreshold stimulus will fire an action potential.  Alteration of ECF Ion Concentrations  Hyperkalemia, brings the membrane closer to the threshold. Now a stimulus that would normally be subthreshold can trigger an action potential.  Hypokalemia, brings the membrane far from the threshold. a stimulus that would normally fire an action potential can not trigger an action potential (need stronger stimulus). Alteration of ECF Ion Concentrations