2401 : Anatomy/Physiology

Transcription

1 Dr. Chris Doumen Week : Anatomy/Physiology Action Potentials NeuroPhysiology TextBook Readings Pages 400 through 408 Make use of the figures in your textbook ; a picture is worth a thousand words! Work the Problems and Questions at the end of the Chapter The principal way neurons communicate is by generating action potentials. Before we proceed, we need to define the following : Depolarization : the membrane potential becomes less negative and sometimes reverses from negative inside to positive inside Repolarization: the voltage difference returns to its orginal state of polarity (negative inside, positive outside). Hyperpolarization: refers to making the MP more negative than the original RMP. Only axons can generate action potentials and the whole event is over in a few milliseconds. As we will see later, muscle cells are also capable of generating action potentials. The capacity to create an action potential is dependent on the presence of special ion channels which can sense a certain membrane potential and then open and close accordingly. These are called voltage gated ion channels. Remember that the resting membrane potential is determined by "plain" leakage ion channels which remain open at all times. Since they remain open at all times, nothing should happen to the membrane potential ; hence the name Resting Membrane potential. Changes in the RMP will however occur when the voltage gated ion channels open or close, hence the name "ACTION" potential. Graded Potentials Before we talk about action potentials, we need to clarify what we mean by graded potentials. These are local depolarizations that do not propagate. They are caused by chemically gated channels. (see diagram). Collin County Community College District It usually involves the opening of chemically gated Na + channels. The influx Na + ions into the cell results in a depolarization. The more channels open, the greater the depolarization ( the graded effect). This depends on the stimulus and thus how many chemicals are present to bind to these channels, and how many channels are present. The Na + ions diffuse under the membrane to all sides and cause local currents and local depolarizations. But this effect dilutes out and the depolarization will decrease in magnitude over distance and eventually dies out. They will vanish unless a new stimulus opens up the chemically gated channels again.

2 2401 : Anatomy/Physiology Page 2 of 6 Action Potentials Action potentials are caused by voltage gated channels. Once initiated, they affect an entire membrane, as long as that membrane has voltage gated channels present. The initial step is a local depolarization that triggers the opening of a voltage gated Na + channel. Just like graded potentials, Na + flows into the cell and causes currents that result in a depolarization in near-by membrane areas. The fact that these near-by areas have voltage gated Na + channels as well, results in opening of these channels and the process repeats itself. It propagates! Threshold level Voltage gated Na+ channels just don t open at any voltage. They are different from the leakage channels in that they respond or open at a certain voltage. This critical level is referred to as the threshold level ( around - 55 mv) There are 4 different phases to recognize during an action potential. 1. Depolarization to threshold level. During stimulation, the Resting Membrane Potential (RMP) gradually depolarizes due to the opening of some chemically gated Na + channels. If this depolarization reaches threshold level at the axon hillock ( where the voltage gated channels start), large numbers of voltage gated Na + channels open. 2. Depolarization Phase A positive feedback system now comes into play Na+ ions rush into according to the electrochemical gradient This will depolarize the Membrane Potential (MP) even more More voltage gated Na + channels will open More Na + rush in and change the MP even further Since there are lots and lots of v.g. Na+ channels, the overall effect is now that the membrane becomes mostly permeable to Na +. Thus, the MP will drift towards the equilibrium potential for Na +, which is +60 mv. However, the v,g, Na + channels close fast when a MP of +30 mv is reached. This signals the end of the depolarization phase. 3. Repolarization phase At the end of the depolarization phase, all the voltage gated K+ channels are open while the v.g Na+ channels close fast. The result is that the influx of Na+ ions comes to a stop.

3 2401 : Anatomy/Physiology Page 3 of 6 At the same time, the voltage gated K+ channels open up. This time the permeability of the membrane switches from one that was permeable to Na+ to one that now has mostly K+ channels open. Thus the MP will shoot towards the Equilibrium Potential for K+. Thus the outflow of K+ ions accelerates. And the MP drops back from + 30 mv towards -86 mv. 4. Hyper-polarization and Restoring the RMP The slow closing action of the K+ channels causes them to close slower, resulting in an excessive outflow of K+ ions even when the RMP has been reached. Thus the MP drifts towards 86 mv but before it gets there, since all channels eventually do close. It is the basis of the slight undershoot or hyper polarization seen. Restoration of the RMP comes about by the action of the Na/K pumps, which bring the RMP back to 70 mv. Refractory Period and v.g. Na+ gates The v.g. Na+ channels have two gates: an upper activation gate and a lower inactivation gate. During the RMP, the activation gate is closed but the inactivation gate is open (see diagram). At treshold, the activation gate opens and Na-ions can rush inside. During the end of phase 2, the inactivation gate closes but the activaion gate remains open. During repolarization, the activation gate closes as well. Finally, at a certain MP, the inactivation gate re-opens and we are back in the orginal position as seen in the diagram. Activation gate In-Activation gate Until the inactivation gate opens ( see diagram), we cannot have another action potential since the channel remains closed, even if the activation gate opens. This period of time from the beginning of the AP until the original state of the v.g. Na+ channel has been re-established is a period during which an excitable cell cannot generate another AP, no matter how strong the stimulus. This is called the absolute refractory period.

4 2401 : Anatomy/Physiology Page 4 of 6 There is a difference in the refractory period among axons Large diameter axons have a RP of ~ 0.4 msec ( can generate 2500 impluses/sec) Small diameter axons have a RP of ~ 4 msec ( up to 250 impulses/sec) What does this mean for our neuronal physiology? Quick and fast information needs to be conducted via large diameter axons ( unless you want a sluggish response ) All or None Principle A stimulus above a threshold stimulus excites a nerve. The size (amplitude) of the response is however independent of the strength of the stimulus. It is the same as lighting a fuse. A match or a blowtorch will start it the same, but it won t have an effect on how fast the fuse will burn! Thus all action potentials are all of the same magnitude. In other words, they all depolarize to + 30 mv no matter what the strength of the stimulus. How do sensory or motor systems respond in different ways? How can they tell the magnitude of a sensory input? The answer is by the firing frequency of the AP. The higher the frequency of the train of AP's, the higher the magnitude of the input impulse. For example, a light pain stimulus will result in low number of AP s per second (low frequency) compared to a high pain stimulus, which will have a higher number of AP s per second ( high frequency). Propagation or the Conduction of an AP Nerve impulses communicate information from one part of the body to another. The information lies in the reversal of the polarity of the Membrane ( the switching from negative to positive inside, and then back to negative inside) or the Action Potential. However, this happens at only one specific area of the neuron. For example, the part of the neuron in your big toe when someone stepped on it. In order to feel the pain, that stimulus must be directed to your brain. It thus needs to travel along the neuron. The AP must travel from the point where it arises to the axon terminals. Once again, this propagation of the signal relies on a positive feedback system. the Na+ ions moving in during the depolarization phase cause positive charge to move to the inside of the membrane Loss of + charge on the surface area will move + charge from adjacent areas to the point of stimulation, so that the adjacent areas become less positive On the inner side of the membrane, influx of + charge diffuses to adjacent areas attracted by the negative charges there This creates local surface currents that slowly depolarize the adjacent membrane areas around the origin of stimulus When this depolarization in the surrounding areas reaches threshold, voltage gated Na+ channels will open in these areas and triggering an AP These events now repeat themselves in the new areas of the membrane

5 2401 : Anatomy/Physiology Page 5 of 6 The action potential will thus travel down the axon analogous to toppling dominoes Excitation at the cell body of the nerve will result in an AP that travels in only one way; towards the axon terminal, since the body or dendrites do not have voltage gated channels. Recent areas of depolarization will still be in a refractory period and thus prevent "back flow" of the action potential movement. The propagation depends on he movement of charges along the inner membrane surface within the axoplasm. Just like our movement is easier in an empty street compared to a crowded street, so is movement of ions along a membrane; it is a function of the resistance it encounters. The smaller the diameter of an axon, the higher the resistance ( more similar charges packed within a smaller cross secretion area). Small diameter axons display thus a slower velocity of conduction then large diameter axons. Speed of Impulse Propagation Rapid reflexes require fast impulse conduction along nerves. A first choice would be large diameter axons ( see above). This is what we see in invertebrates. Their behavior is not complicated and only a few nerves are needed to control their system. However in order to develop a more complex organism, along with a complex behavior system, more nerves are required to channel all the information. Large axons would definitely present a packaging problem within the organism. The problem is solved by keeping axons small and providing them with a myelin sheath ( produced by the Schwann cells or oligodendrocytes). Schwann cells wrap around the axons in many layers in a spiral fashion. The sheath eventually isolates the axon electrically from the outside environment. The encasement is broken at intervals that are called the Nodes of Ranvier. This is the place where the axon is exposed to the extracellular milieu. Nodes Of Ranvier have a very high density of voltage gated Na+ channels. Also, due to the insulation provided by the myelin sheath, the charges on opposite sides of the membrane are further removed with a minimal of charges in-between them. Therefore, the resistance is far

6 2401 : Anatomy/Physiology Page 6 of 6 less for charges to move around needed to depolarize the nodes. The result is a faster moving depolarization phase from node to node. The impulse almost jumps from node to node in myelinated axons in contrast to the continuous movement in un-myelinated axons. This is called Saltatory Conduction. Saltatory conduction goes much faster for a similar diameter axon then continuous conduction. It is also very efficient in terms of energy. Only a small region becomes depolarized, meaning a minimal of Na+ ions inflow and less ATP involved in the Na-K pump activities at these sites to regain the ion distribution. Classification of Nerve fibers They can be classified in 3 categories A fibers : large diameters, myelinated brief refractory period conduct at speeds from 15 to 150 m/sec generally connect CNS with receptors that detect danger in outside environment B fibers: intermediate diameter, myelinated longer refractory period speeds up to 15 m/sec found in nerves that connect viscera to the CNS C fibers : smallest diameter, longest refractory period unmyelinated speeds from 0.5 to 2 m/sec