Action Potential Fall 2024.Stu.pptx

Chapter 3 Action Potential The Cellular Level Guyton and Hall Chapter 5of Organization Lecture Presentation by Abdul J. Lee Rasool Ann Frederick...

Chapter 3 Action Potential The Cellular Level Guyton and Hall Chapter 5of Organization Lecture Presentation by Abdul J. Lee Rasool Ann Frederick University of Texas at Arlington 215 7933 Room BG89 [email protected] u  Student Learning Outcomes Describe voltage and ligand gated channels. Explain the role of voltage-gated channels in an action potential. Describe the phases and ionic basis for the nerve action potential. Describe the refractory period of a nerve. Explain how an impulse is transmitted across an axon. Distinguish between a graded and action potential. Describe saltatory conduction along a myelinated axon.  Most of a neuron’s organelles are in the cell Neuron Structure and Functionbody Dendrites Neurons have dendrites, highly branched Stimulus extensions that receive signals from other neurons Nucleus Presynaptic The axon is a longer extension that cell Axon hillock transmits signals to other cells at synapses Cell An axon joins the cell body at the axon body hillock, it is the site where action potentials Axon form A synapse is a junction between an axon and another cell Synapse The synaptic terminal of one axon passes Synaptic terminals information across the synapse in the form of chemical messengers called neurotransmitters Postsynaptic cell Neurotransmitter Ions and Channels of the neuronal membrane Key Na+ Sodium- potassium Potassium Sodium K+ pump channel channel OUTSIDE CELL OUTSIDE [K+] [Na+] [Cl–] CELL 5 mM 150 mM 120 mM INSIDE [K+] [Na+] [Cl–] [A–] CELL 140 mM 15 mM 10 mM 100 mM INSIDE CELL (a) (b)  Ion Channels in Excitable Tissue Excitable cells can generate an action potential (AP). (e.g. neurons, muscle cells) All cells have a RMP, only excitable cells can modify the membrane potential for other functions, and propagate an AP. A. Ion channels are integral proteins, when open, allows the diffusion of ions. 1. Ion channels are selective; they allow the passage of specific ions. Selectivity is based on the size of the channel and the distribution of charges [amino acids] that line it. For example, a small channel lined with negatively charged groups will allow small cations [+ve] to diffuse and exclude large solutes and anions. 2. Ion channels may be open or closed. When open, ions can flow/diffuse through. When closed ions cannot flow through. 3. The conductance of a channel depends on the probability that the channel is open. The higher the probability that a channel is open,  Consider the Na voltage- Excitable Tissue: Gated channels gated channel below and follow on the next slide a. Voltage-gated channels are controlled by changes in membrane potential/voltage. The activation gate of the neuron Na+ channel is opened at threshold (-55mV), increasing Na+ permeability (e.g., upstroke of the action potential). The inactivation gate of the Na+ channel is closed by b. Ligand-gated depolarization channels (+35mV); Na+ are is regulated by hormones and neurotransmitters. impermeable and repolarization begins. Example, the nicotinic receptor for acetylcholine (ACh) at the NMJ opens when ACh binds to it. The channel is permeable to Na+ and K+, possibly  Na+ Voltage-gated Channel Recording electrode Voltage sensor  Changes in Membrane Potential - terminology 1. Definitions a. Resting membrane is in a polarized state b. Depolarization makes the membrane potential less negative [and positive]. c. During repolarization and hyperpolarization the membrane is more negative. d. Inward current is the flow of charge [ions] into the cell. Positive e. Outward inward current current flow [efflux depolarizes theof positive ions] hyperpolarizes the membrane. f. Action potential membrane potential.is a property of excitable cells (i.e., nerve, muscle, endocrine) that is a rapid depolarization [upstroke], followed by repolarization of the membrane. g. Threshold is the membrane potential at which the action potential begins. At threshold potential, the depolarizing voltage becomes self-sustaining and forms the upstroke of the action potential. Threshold Voltage At threshold: Membrane is depolarized by 15 to 20 mV (from resting potential) Na+ permeability increases owing to a stimulus Na influx exceeds K+ efflux The positive feedback cycle begins Subthreshold stimulus—weak local depolarization that does not reach threshold Threshold stimulus—strong enough to push the membrane potential toward and beyond threshold Action potential is an all-or-none phenomenon—action potentials either happen completely, or not at all Nerve Action Potential Ionic basis of the Nerve Action Potential a. Resting Membrane Potential is approximately −70 mV [-90mV], cell negative. is the result of the high resting conductance to K+ [through leaky K channels], which moves the membrane potential toward the K+ equilibrium potential. At rest, the voltage gated Na+ channels are closed and Na+ conductance is low. The voltage-gated K+ channels are also closed. Ionic basis of the Nerve Action Potential continued b. Upstroke of the action potential (1) Inward current depolarizes the membrane potential to threshold. (2) Depolarization causes rapid opening of the voltage gated Na+ channels, increasing Na+ conductance. (3) The Na+ conductance is higher than the K+ conductance, and the membrane potential is driven toward (but does not quite reach) the Na+ equilibrium potential of +65The (4) mV.overshoot Thus, the rapid is the portion that is positive (> 0mV). depolarization (5) Tetrodotoxinduring the and (TTX) upstroke is lidocaine block voltage-sensitive Na+ channels and caused by an inward Na+ abolish action potentials, resulting in analgesia. current. Ionic basis of the Nerve Action Potential continued c. Repolarization of the action potential (1) Depolarization closes the inactivation gates of the Na+ channels, and the Na+ conductance returns toward zero. (2) Depolarization opens slow voltage- gated K+ channels and increases K+ conductance. (3) The combined effect (TEA) Tetraethylammonium of Na+ channels closing and opening of K+ channels makes blocks the K+K+ these conductance channels. higher than the Na+ conductance, and the membrane is repolarized. Thus, repolarization is caused by an outward K+ current. d. Undershoot (hyperpolarizing afterpotential) The K+ conductance remains high after the RMP is reached. During this time, the membrane potential is driven close to the K+ equilibrium potential.  Key Na+ K+ Rising phase of the action potential Falling phase of the action potential 3 4 Changes in +50 Action ion channels potential Membrane potential 3 during an 0 (mV) 2 4 action –50 Threshold potential Depolarization 1 Resting potential 5 1 2 –100 Time Extracellular fluid Sodium Potassium channel channel Plasma membrane Cytosol Inactivation loop Undershoot Resting state 5 1 Summary Action Potential and Membrane Permeability (Conductance) a. Absolute refractory period time when another AP cannot be elicited, no matter how large the stimulus. Explanation: the inactivation gates of the Na+ channels are closed on depolarization. They remain closed until repolarization occurs. No action potential can occur until the inactivation gates open. b. Relative refractory period begins at the end of the absolute refractory period and continues until the membrane potential returns to the resting level. An action potential is possible if a larger than usual inward +ve current is provided. Explanation: The K+ conductance is high, and the membrane potential is closer to the K+ equilibrium potential and, far from threshold; Recall more inward current will bring the membrane to threshold. An action potential is a regenerating depolarization of membrane potential that propagates along an excitable membrane. [propagates = conducted without decrement] [excitable = capable of 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. Na+ influx causes a patch of the axonal membrane to depolarize Local currents occur Local currents affect adjacent areas in the forward direction Depolarization opens voltage-gated channels and triggers an AP Repolarization wave follows the depolarization wave Na+ channels toward the point of origin are inactivated and not affected by the local currents  Absolute Refractory Propagation of Action Potential Graded Potential Vs Action Potential  Graded Potentials Reflect Stimulus Strength Local current flow is a wave of depolarization that moves through the cell Graded potentials lose strength as they move through the cell due to Current leak Cytoplasmic resistance If strong enough, graded potentials reach the axon hillock where an AP begins. Graded potentials may be excitatory or inhibitory © 2013 Pearson Education, Inc.  Conduction velocity Stimulus Size of voltage (a) In a bare plasma membrane (without voltage-gated channels), as on a dendrite, voltage decays because current leaks across the membrane. Stimulus Voltage-gated ion channel (b) In an unmyelinated axon, voltage-gated Na+ and K+ channels regenerate the action potential along the axon, so voltage does not decay. Conduction is slow because movements of ions and the opening of channel proteins. Stimulus Node of Ranvier Myelin 1 mm sheath Myelin sheath (c) In a myelinated axon, myelin keeps current in axons (voltage doesn’t decay much). APs are generated only in the nodes of Ranvier and jump rapidly from node to node.  In Demyelinated nerve fibers conduction is impaired. A. The demyelinated region of a nerve fiber does not conduct an impulse as well as the myelinated region. Current flow is indicated by the purple arrow. 1. In the myelinated region the high resistance and low capacitance of the myelin allows the local current to move from one node of Ranvier to the next. 2. In a demyelinated axon current is lost through the membrane – decreasing the length constant. (Adapted from Waxman 1982.) B. The density of Na+ and K+ channels differ in the myelinated and demyelinated regions of the axons. 1. Sodium channels are dense at the node of Ranvier but absent in the internodal region of the axon. K+ channels are found beneath the myelin sheath in the internodal regions. 2. The AP conduction properties of the nodal region  Summary of steps involved in action Na equilibrium potential potential As RMP rises Na channels Threshold voltage remain gated Na channels inactivate open d Na All or none Resting membrane channels potential move from inactivate K d to equilibrium closed All the best for the TBL