ACTION POTENTIAL: A CTION POTENTIAL Dr Raghuveer Choudhary Associate Professor Department of Physiology Dr S.N.Medical College Jodhpur The Neuron: The Neuron dendrite cell body (soma) axon terminal (bouton / button) Transmission of information: Transmission of information Information must be transmitted within each neuron and between neurons The Membrane: The Membrane The membrane surrounds the neuron. It is composed of lipid and protein . Ion Channels: Ion Channels Types Ligand-gated Example: neurotransmitters Voltage-gated Open and close in response to small voltage changes across plasma membrane PowerPoint Presentation: Voltage-gated channels – are opened or closed by changes in membrane potential Ligand-gated channels – opened or closed by hormones, second messengers or neurotransmitters. + + + + + Recording Potentials: Recording Potentials The Resting Potential: The Resting Potential There is an electrical charge across the membrane. This is the membrane potential . The resting potential (when the cell is not firing) is a 70mV difference between the inside and the outside. inside outside Resting potential of neuron = -70mV + - + - + - + - + - Ions and the Resting Potential: Ions and the Resting Potential Ions are electrically-charged molecules e.g. sodium (Na+), potassium (K+), chloride (Cl-). The resting potential exists because ions are concentrated on different sides of the membrane. Na + and Cl - outside the cell. K + and organic anions inside the cell. inside outside Na + Cl - Na + K + Cl - K + Organic anions (-) Na + Na + Organic anions (-) Organic anions (-) Forces on ions: + - Forces on ions The electrical voltages and concentration gradients across the membrane exert forces on the ions. For K+ and Cl-, the forces of voltage and concentration are balanced. Organic anions are too large to pass through the membrane. BUT both voltage and concentration forces lead to Na+ entering the cell. inside outside Na + Cl - K + Organic anions (-) Maintaining the Resting Potential: Maintaining the Resting Potential Na+ ions are actively transported (this uses energy) to maintain the resting potential. The sodium-potassium pump (a membrane protein) exchanges three Na + ions for two K + ions. inside outside Na + Na + K+ K+ Na + PowerPoint Presentation: Resting membrane potential is the potential difference across the cell membrane in millivolts (mV). The resting membrane potential is established by different permeabilities or conductances of permeable ions. a. For example, the resting membrane potential of nerve cells is more permeable to K+ than to Na+. b. Changes in ion conductance alter currents, which change the membrane potential. c. Hyperpolarization is an increase in membrane potential in which the inside of the cell becomes more negative. d. Depolarization is a decrease in membrane potential in which the inside of the cell becomes more positive. PowerPoint Presentation: Depolarization – makes the membrane potential less negative (the cell interior becomes less negative) Hyperpolarization – makes the membrane potential more negative Inward current – the flow of positive charge into the cell. Outward current – flow of the positive charge out of the cell. ACTION POTENTIAL: ACTION POTENTIAL Action potential – property of excitable cells that consists of a rapid depolarization or upstroke, followed by repolarization of the membrane potential. Action potentials have stereotypical size and shape, are propagating and are all-or-none. Neuronal firing: the action potential: Neuronal firing: the action potential The action potential is a rapid depolarization of the membrane. It starts at the axon hillock and passes quickly along the axon . The membrane is quickly repolarized to allow subsequent firing. Course of the Action Potential: Course of the Action Potential The action potential begins with a partial depolarization [A]. When the excitation threshold is reached there is a sudden large depolarization [B]. This is followed rapidly by repolarization [C] and a brief hyperpolarization [D]. Membrane potential (mV) [A] [B] [C] [D] excitation threshold Time (msec) -70 +40 0 0 1 2 3 Course of the Action Potential: Course of the Action Potential Threshold – the membrane potential at which the action potential is inevitable. Inward current depolarizes the membrane. If the inward current depolarizes the membrane to threshold, it produces an action potential. Action potentials: Rapid depolarization: Action potentials: Rapid depolarization When partial depolarization reaches the activation threshold, voltage-gated sodium ion channels open. Sodium ions rush in. The membrane potential changes from -70mV to +40mV. Na + Na + Na + - + + - Action potentials: Rapid depolarization: Action potentials: Rapid depolarization Upstroke – inward current depolarizes the membrane potential to threshold. Depolarization causes rapid opening of the activation gates of the Na + channel, and the Na + conductance of the membrane promptly increases. Action potentials: Rapid depolarization: Action potentials: Rapid depolarization Depolarization also closes the inactivation gates of the Na + channel. Depolarization slowly opens K + channels and increases K + conductance to even higher levels than at rest. Repolarization is caused by an outward K + current. Action potentials: Repolarization: Action potentials: Repolarization Sodium ion channels close and become refractory . Depolarization triggers opening of voltage-gated potassium ion channels. K+ ions rush out of the cell, repolarizing and then hyperpolarizing the membrane. K + K + K + Na + Na + Na + + - Step 1: Step 1 Adequate stimulus is applied to a neuron, then the stimulus-gated Na+ channels at the point of stimulus open, Na+ diffuses rapidly into the cell producing a local depolarization Step 2: Step 2 If the magnitude of the depolarization surpasses a limit termed THRESHOLD POTENTIAL (-59 mV), the voltage-gated Na+ are stimulated to open Step 3: Step 3 As more Na+ rushes into the cell, the membrane moves toward 0 mV, then continues to a peak of +30 mV (the + indicates that there is an excess of +ions inside the membrane If the local depolarization fails to cross -59 mV the voltage-gated Na+ do not open and the membrane simply recovers back to the resting potential of -70 mV without producing an action potential Step 4: Step 4 Voltage-gated Na+ stays open for only about 1 ms before automatically closing . This means that once they are stimulated the Na+ always allow sodium to rush in. therefore the action potential is an all-or-nothing response Step 5: Step 5 Once the peak is reached the membrane potential begins to move back toward the resting potential termed REPOLARIZATION surpassing the threshold not only triggers the opening of voltage-gated Na+ but also the voltage-gated K+ these are slow to respond , however, and thus do not begin opening until the inward diffusion of Na+ has caused the membrane potential to reach +30 mV once the K+ are open it rapidly diffuses out of the cell. The outward rush of K+ restores the original excess of + ions on the outside of the membrane, thus repolarizing the membrane Step 6: Step 6 Because the K+ channels remain open as the membrane reaches its resting potential, too many K+ may rush out of the cell. This causes a brief period of hyperpolarization before the resting potential is restored by the action of the Na+-K+ pump and the return of ion channels to their resting state Action potentials: Resuming the Resting Potential: Action potentials: Resuming the Resting Potential Potassium channels close. Repolarization resets sodium ion channels. Ions diffuse away from the area. Sodium-potassium transporter maintains polarization. The membrane is now ready to “fire” again. K + K + K + K + Na + K+ K+ K+ K+ Na+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ IONIC BASIS OF EXCITATION & CONDUCTION: IONIC BASIS OF EXCITATION & CONDUCTION Resting membrane potential- mainly due to leaky K + channels( -70mv) Action potential- it has depolarization, repolarization, after-depolarization and after-hyperpolarization phases. It is mainly due to Na + and K + conductance. PowerPoint Presentation: Catelectrotonic current Surface becomes less positive Reduced potential difference b/w inside & outside Opening of voltage-gated Na + channels Rapid influx of Na + Potential increases towards Na + equilibrium potential PowerPoint Presentation: Na + channels enter inactivated state in few milliseconds Slow opening of voltage-gated K + channel Efflux of K + ions repolarization Sodium-Potassium Exchange Pump: Sodium-Potassium Exchange Pump Gated Ion Channels and the Action Potential: Gated Ion Channels and the Action Potential The Action Potential: The Action Potential The action potential is “all-or-none” . It is always the same size. Either it is not triggered at all - e.g. too little depolarization, or the membrane is “refractory”; Or it is triggered completely. ALL OR NONE RESPONSE: ALL OR NONE RESPONSE The action potential doesn’t occur in a nerve if the stimulus is sub-threshold. If the stimulus is threshold and above, the action potential produced will be of same amplitude, regardless of intensity of stimulus. * The frequency of action potential increases with the increasing intensity of stimulus. Action Potential: Action Potential Refractory Period: Refractory Period Sensitivity of area to further stimulation decreases for a time Parts Absolute Complete insensitivity exists to another stimulus From beginning of action potential until near end of repolarization Relative A stronger-than-threshold stimulus can initiate another action potential PowerPoint Presentation: Absolute Refractory Period Relative Refractory Period -70 mV -85 mV Time in seconds Resting Membrane Potential REFRACTORY PERIOD: REFRACTORY PERIOD Absolute refractory period- it is the period during an action potential, during which a second stimulus can’t produce a second response. Relative refractory period- it is the period during an action potential, during which a stimulus of higher intensity can produce a second response Refractory Period: Refractory Period Is a brief period during which a local area of an axon’s membrane resists restimulation, for about ½ ms after the membrane surpasses the threshold potential IT WILL NOT RESPONSD TO ANY STIMULI NO MATTER HOW STRONG Termed ABSOLUTE REFRACTORY PERIOD REFRACTORY PERIOD: REFRACTORY PERIOD The RELATIVE REFRACTORY PERIOD occurs a few ms after the absolute refractory period This is the time in which the membrane is repolarizing and restoring the resting membrane potential Will only respond to very strong stimuli Conduction of the action potential.: Conduction of the action potential. Passive conduction will ensure that adjacent membrane depolarizes, so the action potential “travels” down the axon. But transmission by continuous action potentials is relatively slow and energy-consuming (Na + /K + pump). A faster, more efficient mechanism has evolved: saltatory conduction. Myelination provides saltatory conduction. PowerPoint Presentation: Propagation of Action Potentials – occurs by the spread of local currents to adjacent areas of membrane which are then depolarized to threshold and generate action potentials. Action Potential Propagation: Action Potential Propagation Action Potential Propagation: Action Potential Propagation Myelination: Myelination Most mammalian axons are myelinated . The myelin sheath is provided by oligodendrocytes and Schwann cells . Myelin is insulating , preventing passage of ions over the membrane. Saltatory Conduction: Saltatory Conduction Myelinated regions of axon are electrically insulated . Electrical charge moves along the axon rather than across the membrane. Action potentials occur only at unmyelinated regions: nodes of Ranvier . Node of Ranvier Myelin sheath Saltatory Conduction: Saltatory Conduction ACCOMODATION: ACCOMODATION When a stimulus is applied very slowly, no matter however strong it might be, it fails to produce an action potential. Cause: a slowly applied stimulus causes slower opening of Na + channels with concomitant opening of K + channels. The influx Na + of is balanced by efflux of K + . PowerPoint Presentation: RHEOBASE - minimum current required to produce action potential. UTILIZATION TIME- time taken for response when rheobase current is applied. CHRONAXIE - time taken for response when twice rheobase current is applied. It is a measure of excitability of tissues. STRENGTH-DURATION CURVE: STRENGTH-DURATION CURVE TIME UTILISATION TIME STRENGTH RHEOBASE 2 X RHEOBASE CHRONAXIE COMPOUND ACTION POTENTIAL: COMPOUND ACTION POTENTIAL Multi-peaked action potential recorded from a mixed nerve bundle is called a compound action potential.