Molecular Mechanism of Action Potential PDF

Molecular Mechanism of action potential Be able to explain, in detail, how K+ and Na+ channels contribute to membrane depolarization, action potentials and hyperpolarization. Understand how to interpret graphs that are part of figure 45.10 in your text, that display changes in membrane potential ass...

Molecular Mechanism of action potential Be able to explain, in detail, how K+ and Na+ channels contribute to membrane depolarization, action potentials and hyperpolarization. Understand how to interpret graphs that are part of figure 45.10 in your text, that display changes in membrane potential associated with ion channel activity. Action Potential [recap] - the change in membrane potential associated with the successful passage of an impulse along a nerve cell [implies that the threshold has been surpassed] action potential is undiminished as it continues down an axon Typical Action Potential [recap] - Vm depolarizes from the resting level of -70 mV to +50 mV and then repolarizes to a level below the original resting level. the episode lasts a few milliseconds the disturbance is propagated undiminished down the axon Characteristics of Action Potential Action potentials are triggered by depolarization A threshold level of depolarization must be reached to trigger an action potential Action potentials are all-or-none events An action potential propagates undiminished throughout an axon After a neuron fires an action potential, there is a brief period, called the refractory period, during which it is impossible to cause another action potential to be produced. This is due to the inactivation of the sodium channels (by the h gate) Action potential threshold (aka all or nothing principle) [recap] - The principle that once the electrical impulse reaches a certain level of intensity (its threshold), it fires and moves all the way down the axon without losing any intensity. Once it crosses the threshold, there is a massive increase in membrane potential (see pic). After the membrane potential drops, there are a few milliseconds where it actually goes below the resting potential (more negative than the baseline), though only temporarily and it quickly returns to resting potential. Depolarization - action potential becomes more positive Hyperpolarization - action potential becomes more negative Hodgkin and Huxley Experiment [recap] - Hodgkin and Huxley had two microelectrodes embedded at different points along the axon to see if a disturbance at an earlier point on the axon could be sensed by the farther end of the axon. They found that 1) If an electrical stimulation is introduced, it causes a major depolarization in that region of the axon. The depolarization only last a short while and in a fraction of a second it goes back to its resting potential [goes positive very quickly, then goes right back down to normal] 2) If the electrical stimulation is large enough, then, a few milliseconds after, the region further along the axon will have a similar depolarization and they just as quickly return to resting potential 3) If sodium (Na)is removed from the system, action potential does not occur Effect of Sodium Removal on the Squid Action Potential Action potential 1: After the first action potential, the solution housing the axon was replaced with one that contained no sodium Action Potential 2-5: As the sodium near the axon membrane declined, the height of the AP declined, and by AP 5, no AP existed. After AP 5, the sodium-containing medium was re-introduced, and the normal AP could be fired (AP 6) - Big Picture: sodium plays a critical role in depolarization Basic structure of action potential curve 1. Resting stage (baseline) 2. depolarization (massive spike) 3. repolarization (spike goes down) 4. Undershoot (hyperpolarization; goes below the baseline) 5. resting stage (return to baseline) Voltage-gated Sodium Channel - A membrane protein forming a pore that is permeable to Na+ ions and gated by depolarization of the membrane. The channel exists in three states A) Closed (m gate) B) Open (m gate) C) Inactive (h gate; only last a few milliseconds) Two Gates M gate: Location inside the channel where amino acids on opposite ends will join together blocking any ion movement into the channel H gate: Cluster of amino acids at the very end of the intracellular part of the membrane Stages At rest (no axon activity [-70 mV]) m gate is closed but h gate remains open - m gate is opened in response to a change in membrane potential (voltage-gated pathway Does NOT allow Na+ inside the cell Opening of the channel (immediately after depolarization) m gate and h gate are open Na+ flows into the cell Inactivation (5 ms after depolarization) m gate is open but h gate is closed+6 Does NOT allow Na+ inside the cell While inactivated, the channel cannot be opened, regardless of the membrane potential. This is the basis of the refractory period of an axon that follows an action potential, which is the time during which another action potential cannot be elicited Lack of the flow of Na+ leads to repolarization and eventually hyperpolarization Status of m and h gate in sodium channels - When the axon is at rest (not sending a signal), m gate is (open/closed) and h gate is (open/closed) When the sodium channel permitting the flow of Na+, m gate is (open/closed) and h gate is (open/closed) During the refractory period, m gate is (open/closed) and h gate is (open/closed) Refractory period - Very short time frame when the sodium channel cannot be opened and so another action potential cannot be elicited the channel remains closed regardless of membrane potential Occurs b/ the h-gate is closed 5 ms after depolarization Refractory period ends once the h-gate opens up again Delayed-Rectifier Potassium Channel - Allow ions one way and take some time to open. It is responsible for the recovery of the membrane potential to the starting level, or even more negative than the starting level Only two states: open and closed One Gates - m gate: Location inside the channel where amino acids on opposite ends will join together blocking any ion movement into the channel It opens in response to membrane depolarization, but with a slight delay compared to the voltage-gated sodium channel. Stages - At rest (no axon activity [-70 mV]) m gate is closed No flow of K+ Immediately after Depolarization m gate is closed No flow of K+ no change even though there was a change in membrane potential from the Na+ entering the cell (recall this is a delayed pathway) 2 ms after Depolarization m gate is OPEN change in membrane potential had a delayed effect K+ flows out of the cell -- the cell depolarizes often the cell is depolarized to below the starting level (undershoot) undershoot - The part of an action potential when the membrane potential is more negative than at rest hyperpolarization - Overcoming undershoot The inactivation (h) gate of the sodium channel must open before the channel returns to the resting state. Until that occurs, an action potential cannot be generated idk if this depolarizes back to resting potential since i think the sodium channel is still closed??? Interplay between voltage-gated sodium channels and delayed-rectifier potassium channels A) Resting Potential: both sodium and potassium channels are closed - Sodium channel: m gate closed and h gate open Potassium channel: m gate closed B) Depolarization phase: sodium channel is open; potassium channel remains closed (due to delayed response) - Sodium channel: m gate open and h gate open Potassium channel: m gate closed C) Repolarization Phase: sodium channel is closed; potassium channel is open - Sodium channel: m gate open but h gate closed [inactive state] Potassium channel: m gate open (activated by Na+ entering the cell and changing the membrane potential) D) Hyperpolarization phase (Undershoot): sodium channel is closed; potassium channel is open - Sodium channel: m gate open but h gate closed [inactive state] Potassium channel: m gate open E) Return to Resting Potential: sodium channel is closed (i think, this one weird here???); potassium channel is closed - Sodium channel: m gate closed but h gate opens up [no longer in the inactive state] The inactivation (h) gate must open before the channel returns to the resting state. Until that occurs, an action potential cannot be generated - Potassium channel: m gate closed The conductance (permeability) of the membrane to Na and K during an action potential The permeability to a particular ion is determined by the number of open channels for that ion. Na channels peak during the depolarization of the action potential K channels peak during the repolarization of the action potential motor neuron [recap] - - multipolar neurons that carry outgoing information from the brain and spinal cord to the muscles that use them to contract. Neural cells have their cell bodies in the ventral part (towards the stomach) of the spinal cord and send long neurites to the muscles. They are not derived from neural crest cells but from the neural tube. Dendrites receive information from other neurons. Information is collected up in the cell body. Axon sends the signal to the periphery tissues (in this case, muscle tissues) Information goes from spinal cord to periphery Motor unit - a motor neuron and all the muscle fiber it stimulates junction between the motor neuron and the muscle fiber is the neuromuscular junction Every motor neuron in the spinal cord innervates one muscle fiber. An action potential generated in the neuron leads to the contraction of the muscle. The axon of the motor neuron may be a meter long. - We are studying the processes that lead to the creation of a action potential in the neuron and the spread of the AP down the axon - flow of action potential down the axon Yellow = sodium channel Blue = potassium channel - - - Stimulation from electrical current changes the shape of a Na+ channel (opening the m gate) allowing Na+ to rush inside the axon Na+ accumulates inside the membrane and travels down the axon, which causes a change in the electrical properties leading to depolarization in further parts of the axon. When these areas undergo depolarization, Na+ against rushes into the axon causing an action potential further along the axon. That increased Na+ continues traveling further down the axon Once the Na+ accumulation has passed on down the axon, the K+ channels begin their delayed activation in the area where the Na= accumulation just was. K+ channels push K+ out of the axon contribution to repolarization/hyperpolarization. Eventually these close and that area returns to baseline potential. This process keeps on continuing down the axon Be able to explain why action potentials, once initiated, can only travel in one direction. Why does the action potential only move away from the cell body? - Because once the action potential has occurred in a region, the refractory period in the sodium channels occur (inactive state [h gate]) and so sodium cannot be transported across the membrane where the action potential had already passed through for a couple milliseconds (movement of sodium is time-dependent) Be particularly familiar with the structure and function of Schwann cells. Know what the term “Saltatory conduction” means. Schwann cells - Type of glial cell (neural supporting cell) that surrounds the axon by producing an insulating layer of myelin important for increasing the speed with which neural signals travel through saltatory conduction Structure: - Wraps around axons in circular layers Node of Ranvier: segments of the axon not covered by Schwann cells myelin - - A layer of fatty tissue segmentally encasing the fibers of many neurons; enables vastly greater transmission speed of neural impulses as the impulse hops from one node to the next. produced by Schwann cells saltatory conduction - - Rapid transmission of a nerve impulse along an axon, resulting from the action potential jumping from one node of Ranvier to another, skipping the myelin-sheathed regions of the membrane. no Na+ or K+ channels present in the myelinated areas action potential/refractory period only occurs at Nodes of Ranvier Myelination allows axons to have small diameters, yet transmit action potentials rapidly synapse - the junction between the axon tip of the sending neuron and the dendrite or cell body of the receiving neuron the site where an axon makes contact with another cell Be familiar with the types of ion channels that are stimulated by the excitatory presynaptic axons and the inhibitory presynaptic axons. Understand how these two types of axons cause different changes in the membrane potential and how these signals are integrated at the axon hillock. presynaptic neuron - neuron that sends the signal postsynaptic neuron - neuron that receives the signal How are action potentials initiated? 1) The dendrites on the cell body receive inputs from the axons of presynaptic neurons at the synapse --- The inputs into a neuron from another axon can be either excitatory (favors forming action potential) or inhibitory (disfavors forming action potential), depending on the ion channels that are opened at the synapse. 2) The axon releases a chemical messenger at the synapse that binds to receptors on the postsynaptic cell and opens ions channels. --- In general, the opening of Na+ channels or Ca+ channels is excitatory, while the opening of Cl channels is inhibitory 3) Information from the other neurons get collected in the spike-initiating zone and either creates an action potential or doesn't --- adds up the signals from excitatory presynaptic neurons (favors forming action potential) and inhibitory presynaptic neurons (disfavor forming action potentials) and if the AP threshold is met then an AP will occur --- if the threshold is not met, the change in membrane potential will not continue down the axon --- adds up all the EPSP (signals that favor forming an action potential) and all the IPSP (signals that disfavor forming an action potential) Excitatory Presynaptic Neuron Presynaptic neurons that favor depolarization and generating a new action potential. The influx of Na+ increases membrane potential. The excitatory presynaptic axon targets the excitatory synaptic current on the dendrite of the postsynaptic neurons. This activates the opening of Na+ or Ca+ channels at the synapse. The opening of these channels stimulate depolarization which will favor the formation of an action potential Inhibitory Presynaptic Neuron Hyperpolarizes and makes it more difficult for an impulse to cross synapse. The influx of Cldecreases the membrane potential. --- initiate inhibitory signals (disfavor action potential) Mechanism (see term above for pic) The inhibitory presynaptic axon targets the inhibitory synaptic current on the dendrite of the postsynaptic neurons. This activates the opening of Cl- channels at the synapse. The opening of these channels stimulate hyperpolarization which disfavors the formation of action potential spike-initiation zone (aka axon hillock) - - A region of the neuronal membrane near the base of the axon where action potentials are normally initiated, characterized by a high density of voltage-gated sodium channels. Several dendrites will send either excitatory or inhibitory signals. The signals will congregate at the spike-initiation zone and be added up. If the AP threshold is met then an AP will occur. If not, the change in membrane potential will not continue down the axon. adds up all the EPSP (signals that favor forming an action potential) and all the (signals that disfavor forming an action potential) EPSP Excitatory postsynaptic potential - positive charge a slight depolarization of a postsynaptic cell, bringing the membrane potential of that cell closer to the threshold for an action potential. IPSP Inhibitory postsynaptic potential - negative charge a slight hyperpolarization of the postsynaptic cell, moving the membrane potential of that cell further from threshold. Understand the concepts of spatial and temporal summation, and be able to give an example of each. Ways EPSP and IPSP can contribute to reaching action potential threshold 1) spatial summation 2) temporal summation spatial summation - If two different inputs arrive at the same time, their effects on the membrane potential of the spike initiating zone are cumulative. If enough different inputs arrive at the same time, the spike initiating zone’s membrane potential can be brought to the threshold. Determined by the combined effect of EPSPs or IPSPs produced nearly simultaneously by different synapses. if each of the charges occurred individually, none of them would be strong enough to form an action potential. But, if they are done at the same time, they can be added and can then overcome the threshold. temporal summation - - The synaptic potential decays slowly, so if the second pulse arrives soon after the first, its effect on membrane potential is additive. Differs from spatial summation in that the signals are not occurring at the exact same time, but in succession after one another, though still fast enough for the change in the potential to not go back down before the next stimulation starts. the same amount of stimulation, but they happen so quickly after one another minuscule difference in time between stimulation Flow of action potential from motor unit to the muscle fiber pretty much incorporate everything we learned above that's a lot of writing and i don't want to do it synaptic inputs on a neurons - The mapping of a portion of the actual inputs to a single neuron. Some of these inputs will be excitatory, some inhibitory. The neuron integrates the totality of the inputs, and if the spike initiating zone is depolarized to threshold, an action potential is produced. this took way lon ger than it should have