Action Potential Physiology PDF

PHYSIOLOGY | Block 1.8 ACTION POTENTIAL Dr. Diana May Laraya September 4, 2023 | 7:30-9:30 Transcribed by: Robles, Sumile, Yañez OUTLINE I. Neuron action potential a. Resting Stage b. Depolarizatio...

PHYSIOLOGY | Block 1.8 ACTION POTENTIAL Dr. Diana May Laraya September 4, 2023 | 7:30-9:30 Transcribed by: Robles, Sumile, Yañez OUTLINE I. Neuron action potential a. Resting Stage b. Depolarization Stage c. Repolarization Stage II. Voltage-gated Na+ and K+ Channels a. Activation and Inactivation of the Voltage-Gated Na+ b. Voltage-Gated K+ Channel and Its Activation III. Summary of Events that Cause the Action Potential IV. Propagation of the Action Potential Resting Potential a. All-or-Nothing Principle V. Re-establishing Na+ and K+ Ionic The resting stage is the resting membrane Ingredients After Action Potentials are potential BEFORE the action potential Completed – Importance of Energy begins. Metabolism VI. Plateau in Some Action Potentials What happens to the membrane? VII. Rhythmicity of Some Excitable Tissues o It is “polarized” due to the −70 mV – Repetitive Discharge negative membrane potential that is VIII. Excitation – The Process of Eliciting present. Action Potential IX. Refractory Period After an Action Depolarization Stage Potential, During Which a New Stimulus Cannot Be Elicited What happens to the membrane? o It is depolarized due to the inflow of Na+ ions that increases the potential NEURON ACTION POTENTIAL rapidly in the positive direction. Nerve signals are transmitted by action How depolarization happens? potentials o The membrane becomes permeable o rapid changes in the membrane to Na+ ions allowing rapid diffusion of potential that spread rapidly along these ions to the interior of the axon. the nerve fiber membrane o The normal polarized state if -70 mV Each action potential begins with a is immediately neutralized. sudden change from the normal resting negative membrane potential to positive Depolarization in large nerve fibers potential and goes back to its original o The potential overshoot beyond the state. zero level due to great excess of Na+ ions moving interiorly. Depolarization in small nerve fibers and many CNS neurons o The potential merely approaches the zero level and does not overshoot to the positive state due to great excess of Na+ ions moving interiorly.  Right figure: Inactivated Na+ Channel Repolarization Stage o The membrane potential is decreasing from 0 to −70 mV. What happens to the membrane? o There is a sudden conformational change o It is repolarized due to the rapid in the inactivation gate making it close. diffusion of K+ ions that re- a. Na+ ions can no longer pour to the establishes the normal negative interior through the channel. resting membrane potential. b. The membrane begins to repolarize o Slower process How repolarization happens? o After the membrane becomes highly permeable to Na+ ions, Na+ channels Remember: begin to close, and the K + channels o Inactivation gate will not reopen until open Remember to a greater degree membrane potential returns to or near than normal. the original membrane potential. o Usually not possible for the sodium channels to open again without first repolarizing the nerve fiber. VOLTAGE-GATED Na+ AND K+ CHANNELS Na+ (Sodium) Channels K+ (Sodium) Channels This channel has two gates: 1. Activation gate – near the outside 2. Inactivation gate – near the inside Left figure: Normal Resting Membrane o The membrane potential is −70 millivolts. o The gate is closed, which prevents any entry of K+ ions to the exterior. Middle figure: Activated K+ Channel Left figure: Normal Resting Membrane o The membrane potential is rising from o The membrane potential is −70 millivolts. −70 mV toward 0. o The activation gate is closed, which o There is a sudden conformation change in prevents any entry of Na+ ions to the the channel making it open. interior of the fiber through these sodium a. K+ ions can pour outward through channels. the channel. o Slight delay in the opening of channel Middle figure: Activated Na+ Channel a. They are open for most part at o The membrane potential is rising from about the same time that the Na+ −70 mV toward 0 (around -55mV). channels are beginning to close o There is a sudden conformation change in because of the inactivation. the activation gate making it open. a. Na+ ions can pour inward through Remember: the channel, increasing the sodium o The decrease in Na+ entry to the cell permeability. and the simultaneous increase in K+ exit combine to speed the repolarization process – full recovery of the resting membrane potential. SUMMARY OF EVENTS THAT CAUSE THE ACTION POTENTIAL PROPAGATION OF THE ACTION POTENTIAL A. Normal resting nerve fiber B. Nerve fiber that has been excited in its midportion, which suddenly develops The bottom of the figure shows the changes increased permeability to sodium. (Arrows in membrane conductance for sodium and show a local circuit of current flow from the potassium ions. depolarized areas of the membrane to the During the resting state, before the action adjacent resting membrane areas.) potential begins, the conductance for C. Sodium channels in these new areas potassium ions is 50 to 100 times as great as immediately open. the conductance for sodium ions. D. Explosive action potential spreads At the onset of the action potential, the sodium channels almost instantaneously Nerve/ Muscle Impulse – transmission of the become activated and allow up to a 5000-fold depolarization process along the entire length of the increase in sodium conductance. fiber. The inactivation process then closes the sodium channels within another fraction of a All-or-Nothing Principle millisecond. The onset of the action potential also initiates voltage gating of the potassium Once an action potential has been elicited at channels, causing them to begin opening any point on the membrane of a normal fiber, the more slowly, a fraction of a millisecond after depolarization process travels over the entire the sodium channels open. membrane if conditions are right, but it does not At the end of the action potential, the return of travel at all if conditions are not right. the membrane potential to the negative state causes the potassium channels to close back Safety factor for propagation - for continued to their original status but, again, only after an propagation of an impulse to occur, the ratio of action additional millisecond or more delay. potential to threshold for excitation must at all times During the early portion of the action be “greater than 1” potential, the ratio of sodium to potassium conductance increases more than 1000-fold. The “Voltage Clamp” Method for Measuring the THIS REQUIRES ATP (Active metabolism) Effect of Voltage on Opening and Closing of the Voltage-Gated Channels. PLATEAU IN SOME ACTION POTENTIALS Used to measure the flow of ions through the different channels. Two electrodes are inserted into the nerve fiber. One of these electrodes is used to measure the voltage of the membrane potential, and the other is used to conduct electrical current REMEMBER!! Initiation of the Action Potential 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 channels to begin opening causes a POSITIVE- FEEDBACK CYCLE OR SODIUM Within another fraction of a millisecond, the rising membrane potential causes CLOSURE of the sodium channels and opening of potassium channels, and the action potential soon terminates. Sometimes the potential remains on a Threshold for Initiation of the Action Potential plateau near the peak of the spike potential An action potential will not occur until the for many milliseconds initial rise in membrane potential is great ▪ and only then does repolarization enough to create the positive feedback. begin. A sudden rise in membrane potential of 15 The plateau greatly prolongs the period of to 30 millivolts is usually required. depolarization. Level of −65 millivolts is said to be the This type of action potential occurs in heart threshold for stimulation. muscle fibers, where the plateau LASTS FOR AS LONG AS 0.2 TO 0.3 SECOND and Propagation of the Action Potential causes contraction of heart muscle to last for Propagation of action potentials in both this same long period. directions along a conductive fiber. Factors causing this plateau Excitable membrane has no single direction ▪ First, in heart muscle, two types of of propagation. channels enter the depolarization process: RE-ESTABLISHING NA+ AND K+ IONIC ❖ The usual voltage-activated INGREDIENTS AFTER ACTION POTENTIALS sodium channels, called fast ARE COMPLETED – IMPORTANCE OF channel ENERGY METABOLISM ❖ Voltage-activated calcium- sodium channels, which are Re-establishing the sodium and potassium slow to open and are membrane concentration differences is called slow channels. achieved by action of the Na+-K+ pump in the ❖ Opening of fast channels same way as described previously for the causes the spike portion of the original establishment of the resting potential action potential, whereas the to return to their original state. slow, prolonged opening of the Its degree of activity is strongly stimulated slow calcium-sodium channels when excess sodium ions accumulate mainly allows calcium ions to inside the cell membrane. enter the fiber, WHICH IS LARGELY RESPONSIBLE  FOR THE PLATEAU Re-excitation Process Necessary for PORTION OF THE ACTION Spontaneous Rhythmicity. POTENTIAL AS WELL. ▪ Second that may be partly responsible For spontaneous rhythmicity to occur, the for the plateau is that the voltage- membrane even in its natural state must be gated potassium channels are slower permeable enough to sodium ions to allow than usual to open, often not opening automatic membrane depolarization. Thus, very much until the end of the plateau. Figure 5–14 shows that the “resting” ❖ delays the return of the membrane potential in the rhythmi-cal control membrane potential toward its center of the heart is only –60 to –70 milli- normal negative value of –80 volts. This is not enough negative voltage to to –90 millivolts. keep the sodium and calcium channels totally closed. Therefore, the following sequence occurs: RHYTHMICITY OF SOME EXCITABLE ▪ Some sodium and calcium TISSUES—REPETITIVE DISCHARGE ions flow inward ▪ This increases the membrane voltage in the positive Repetitive self-induced discharges occur direction, which further normally in the heart, in most smooth muscle, increases membrane and in many of the neurons of the central permeability nervous system. These rhythmical discharges ▪ Still more ions flow inward cause: ▪ The permeability increases ▪ the rhythmical beat of the more and so on, until an action heart potential is generated. ▪ hythmical peristalsis of the ▪ Then, at the end of the action intestines potential, the membrane re- ▪ such neuronal events as the polarizes. rhythmical control of breathing. ▪ After another delay of Almost all other excitable tissues can milliseconds or seconds, discharge repetitively if the threshold for spontaneous excitability stimulation of the tissue cells is reduced low causes depolarization again, enough. and a new action potential occurs spontaneously. This cycle continues over and over and causes self-induced rhythmical excitation of the excitable tissue. toward the end of each action potential, and continuing for a short period thereafter, the membrane becomes excessively permeable to potassium ions. The excessive outflow of potassium ions carries tremendous numbers of positive charges to the outside of the membrane, leaving inside the fiber considerably more negativity than would otherwise occur. This continues for nearly a second after the preceding action potential is over, thus drawing the membrane potential nearer to the potassium Nernst potential. ▪ This is a state called hyperpolarization. ▪ As long as this state exists, self-re-excitation will not occur. But the excess potassium conductance gradually  disappears, thereby allowing normal resting electrical the membrane potential again voltage across the membrane. to increase up to the threshold ▪ Negative current from the for excitation electrode decreases the Then a new action potential results, and the voltage on the outside of the process occurs again and again. membrane to a negative value nearer to the voltage of the negative potential inside the EXCITATION-THE PROCESS OF fiber. ELICITING THE ACTION POTENTIAL ❖ This decreases the electrical voltage Any factor that causes sodium ions to begin across the membrane to diffuse inward through the membrane in and allows the sodium sufficient numbers can set off automatic channels to open, regenerative opening of the sodium channels. resulting in an action ▪ can result from mechanical potential. disturbance of the membrane, ❖ Conversely, at the chemical effects on the positive electrode, the membrane, or passage of injection of positive electricity through the charges on the outside membrane. of the nerve membrane ▪ All these are used at different heightens the voltage points in the body to elicit difference across the nerve or muscle action membrane rather than potentials: lessening it. ❖ mechanical pressure to ▪ This causes a state of excite sensory nerve hyperpolarization, which endings in the skin decreases the excitability of ❖ chemical the fiber rather than causing neurotransmitters to an action potential. transmit signals from one neuron to the next Threshold for Excitation, and Acute Local in the brain ❖ and electrical current to Potentials. transmit signals between successive A weak negative electrical stimulus may not muscle cells in the be able to excite a fiber. heart and intestine ▪ However, when the voltage of the stimulus is increased, Excitation of a Nerve Fiber by a Negatively there comes a point at which Charged Metal Electrode excitation does take place. ▪ These local potential changes The usual means for exciting a nerve or are called acute local muscle is to apply electricity to the nerve or potentials, and when they fail muscle surface through two small electrodes to elicit an action potential, ▪ one is negatively charged they are called acute ▪ the other positively charged. subthreshold potentials. When this is done, the excitable membrane becomes stimulated at the negative electrode. The cause of this effect is the following: ▪ the action potential is initiated by the opening of voltage- gated sodium channels. Further, these channels are opened by a decrease in the  Absolute refractory period ▪ The period during which a second action potential cannot be elicited, even with a strong stimulus ▪ This period for large myelinated nerve fibers is about 1/2500 second. ❖ such a fiber can transmit a maximum of about 2500 impulses/s Inhibition of Excitability—Stabilizers and Local Anesthetics Other factors, called membrane-stabilizing factors, can decrease excitability. ▪ For instance, a high extracellular fluid calcium ion concentration decreases This figure shows that even a very weak membrane permeability to stimulus causes a local potential change at sodium ions and the membrane, but the intensity of the local simultaneously reduces potential must rise to a threshold level before excitability. Therefore, calcium the action potential is set off. ions are said to be a “stabilizer.” “REFRACTORY PERIOD” AFTER AN Local Anesthetics. ACTION POTENTIAL, DURING WHICH A NEW STIMULUS CANNOT BE Among the most important stabilizers are the ELICITED many substances used clinically as local anesthetics, including procaine and A new action potential cannot occur in an tetracaine. excitable fiber as long as the membrane is ▪ Most of these act directly on still depolarized from the pre-ceding the activation gates of the action potential. sodium channels, making it ▪ The reason for this is that much more difficult for these shortly after the action gates to open, thereby potential is initiated, the reducing membrane channel becomes inactivated, excitability. and no amount of excitatory ▪ When excitability has been signal applied to these reduced so low that the ratio of channels at this point will open action potential strength to the inactivation gates. excitability threshold (called ▪ The only condition that will the “safety factor”) is reduced allow them to reopen is for the below 1.0, nerve impulses fail membrane potential to to pass along the anesthetized return to or near the original nerves. resting membrane potential level. ▪ Then, within another small fraction of a second, the inactivation gates of the channels open, and a new action potential can be initiated.