Collin County Community College BIOL 2401 Week 5 Nervous System II 1 The Membrane Potential Question : Is the Equilibrium Potential a set number or can it change? Let s look at the Nernst Equation again. E x = - {60/z}. log {[X in ]/[X out ]} Which of the parameters in this equation are subject to change? The internal concentration of a cell is pretty much fixed on a short term basis, but the external ( interstitual fluid.. plasma ) one can be changed rapidly. For example : Intravenous injections! 2 1
The Membrane Potential Question : If a cell had equal numbers of Na + and K + leakage channels, what would the resting membrane potential become? In this case, the membrane potential will drift to the average between the two Equilibrium potentials : MP = (E k + E Na ) /2 = (- 87 + 60 ) /2 = (-27)/2 = -13.5 mv [K + ] + - + - + - [K + ] - + [Na + ] [Na + ] But a typical cell has on average 50 x more K + leakage channels than it has Na + leakage channels! (the membrane potential will drift to the Eq. Pot. For K + ) 3 The Membrane Potential If a normal cell membrane was suddenly only permeable to K +, the membrane potential would drift and become equal to the E.P. for K + 4 2
The Membrane Potential If a normal cell membrane was suddenly only permeable to Na +, the membrane potential would drift and become equal to the E.P. for Na + 5 The Resting Membrane Potential The resting membrane potential is the membrane potential of an undisturbed cell. The membrane potential is however influenced by the opening and closing of ion channels and is therefore a dynamic entity. Membrane contains Passive (leak) channels that are always open Active (gated) channels that open and close in response to stimuli Chemically regulated channels Voltage-regulated channels Mechanically regulated channels 6 3
The Resting Membrane Potential 7 The Resting Membrane Potential The opening of previously closed channels will influence the membrane potential since it lowers the resistance for entry (or exit) of certain ions according to the electrochemical forces acting on it. Definitions Any shift from the resting membrane potential (RMP) towards a 0 mv is called a depolarization The movement of a depolarized membrane potential back towards the normal RMP is called a repolarizartion An increase in the negativity of the RMP is called a hyperpolarization. 8 4
TransMembrane Potential Changes 9 TransMembrane Potential Changes There are two types of Transmembrane Potential changes we need to be aware of! Graded Potentials : These are localized and do not propagate themselves. They are created by chemically gated or mechanically gated ion channels. Action Potentials : These are created by voltage gated ion channels. Since these channels respond to voltage to open or close, and since ion flow results in voltage changes, these potential changes tend to propagate ( results in a positive feedback system of opening more channels). 10 5
Graded Potentials These are membrane potential changes that remain localized in a certain area of a membrane Usually the result of a chemically gated channel that opens in the membrane. Channels are closed 11 Graded Potentials Channels are opened by binding of a chemical ( ) This causes a sudden increase in a specific ion flow. In this case, Na+ enters and it results in a local depolarization ( went from - 70 to - 65 mv). The more channels open, the greater the depolarization. 12 6
Once under the membrane, the ion causes a current under the membrane since it is attracted by opposite charges on both sides. Here, Na+ moves to left and right and results in local depolarizations on either side of its point of entry. The depolarization is not as much since the ions are diluted the more the move away. 13 Graded Potentials The size of a graded potential (here, graded depolarizations) is proportionate to the number of channels that open ( related to the intensity of the stimulus). Eventually, graded potentials decay over distance. 14 7
Action Potentials Action Potentials are the result of opening and closing of 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! 15 Action Potentials and Treshold Voltage gated Na + channels don t open at any voltage change. The depolarization needs be large enough such that the Membrane Potential reaches a certain value before they open. This value of the MP is called the Threshold value Once the Threshold value is reached, all voltage gated Na + channels that experience that voltage will open That Threshold value is between -60 and - 55 mv. 16 8
Steps during Action Potentials Important to Remember. Nerve cells have 50 x more K+ leakage channels than Na+ leakage channels In the axons, Nerve cells have a whole lot more voltage gated Na+ and K+ channels. As long as these voltage gated channels are closed, they may as well not be there. BUT, when they open, they will change the permeability characteristic of the membrane. They suddenly will lower the resistance for certain ions to move. 17 Steps during Action Potentials Step 1. There is a resting membrane potential of about - 70 mv. This RMP is maintained by leakage channels and Na-K pump. A stimulus causes a small depolarization As long as treshold is NOT reached, nothing will happen. Area where v.g. channels start to occur 18 9
Steps during Action Potentials If the depolarization over the cell body reaches threshold at the axon hillock, we will activate the v.g. Na+ channels in that area. The spread of the depolarization over the cell body is only via Graded potentials mentioned earlier. There are no v.g. channels in the cell body membrane! 19 Steps during Action Potentials Step 2. The voltage gated Na+ channels have two gates. At the RMP, the lower gate is open ( called the inactivation gate), but the upper gate ( the activation gate) is closed. With depolarization reaching threshold, the activation gate opens as well and Na+ rushes into the cell. Since at this point, ALL voltage gated Na+ channels are affected, the permeability for Na+ is maximum. The result it thus a fast depolarization. 20 10
Steps during Action Potentials This depolarization is an ALL or NONE effect. If threshold is not reach, nothing (NONE) happens. If treshold is reached, ALL v.g. Na+ channels open. 21 Steps during Action Potentials Why do we get a depolarization? When ALL the Na+ channels open, the MP will drift towards the Equilibrium Potential for Na+ ( = + 60 mv) 22 11
Steps during Action Potentials Step 3. Once a MP of +30 mv is reached, the inactivation gate closes and the depolarization phase comes to an end. At the same time, voltage gated K+ channels become activated and open up. 23 Steps during Action Potentials The massive opening of v.g. K+ channels results in K+ moving out of the cell. Now the cell is massively leaky to K+. The results is a quick re-polarization back towards the Equilibrium Potential for K+ (being -87 mv) 24 12
Steps during Action Potentials Step 4 and 5. The v.g. K + channels do not close all at the same time. The results is that the MP keeps drifting towards the K + EP. The MP will overshoot the RMP and show a hyperpolarization. 25 Steps during Action Potentials Step 4 and 5. There is now extra Na + in the cell and extra K + has left the cell. Order is restored by the Na-K pump, bringing the MP back to the original value = resting membrane potential. 26 13
Steps during Action Potentials 27 Steps during Action Potentials 28 14
Action Potentials and Refractory Period Activation gate of v.g. Na+ channels In-Activation gate There is a time during re-polarization when both gates on the voltage gated Na+are closed. The RMP needs to reach a certain repolarization voltage before one of the gates opens up again. Thus there is a certain period when the v.g. Na+ channel cannot open again because both gates are closed and the inactivation gates needs to be primed again to open! 29 Action Potentials and Refractory Period Activation gate of v.g. Na+ channels In-Activation gate Thus, since an action potential starts with the opening of V.G. Na+ channels, NO action potential is possible during this time period. This is called the Absolute Refractory Period Starts from the time the action potential begins until right after the threshold level has been passed again. 30 15
Action Potentials and Refractory Period 31 Propagation of Action Potentials At the point of the first A.P, Na+ ions enter and spread under the membrane by local currents This will cause local depolarizations and new v.g. Na+ channels will open in the areas downstream ( see arrow) from the starting point. The result is a new A.P. No A.P. will be possible upstream, since the v.g. Na+ channels are in a refractory state! 32 16
Propagation of Action Potentials 33 Propagation of Action Potentials The propagation of an A.P. in an axon is thus a one way process. From axon hillock towards the axon terminal. It thus resembles falling dominos. The only way this can repeat itself is if we raise each domino again (= refractory period of each channel) 34 17
Propagation of Action Potentials There is a difference in the refractory period among axons Large diameter axons have a RP of ~ 0.4 msec ( can generate 2500 impulses/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 ) 35 Propagation of Action Potentials 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 under 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. 36 18
Propagation of Action Potentials Rapid reflexes require fast impulse conduction along nerves. A first choice would be large diameter axons. This is what one sees in many lower organisms. 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 were required to channel al the information. Large axons would definitely present a packaging problem within the organism. 37 Propagation of Action Potentials Huge skull - Packed with large diameter axons? 38 19
Myelination and Action Potentials The problem was solved by keeping axons small and providing them with a myelin sheath (produced by the Schwann cells or oligodendrocytes The sheath 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. 39 Myelination and Action Potentials 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 less for charges to move around from node to node. 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. 40 20
Myelination and Action Potentials In saltatory conduction, action potentials jump from node to node 41 Myelination and Action Potentials Loss of myelination results in current leak and slower conductions 42 21
Conduction velocity in axons A fibers : large diameter and myelinated B fibers : intermediate diameter and myelinated C fibers : small diameter and un-myelinated 43 ALL or Nothing Principle When an action potential occurs, ALL v.g. Na+ channels open and the MP drift towards + 60 mv. But, at + 30 mv, ALL v.g. Na+ channels close. No matter how strong the stimulus, from the moment we reach threshold, the amplitude of the Action potential is always + 30 mv. So how does the body distinguish if we are dealing with a small impulse or a large impulse? 44 22
ALL or Nothing Principle The answer lies in the frequency of Action potentials generated. A weak impulse generates few action potentials per time unit and releases thus few neurotransmitters. 45 ALL or Nothing Principle A stronger impulse generates more action potentials per time unit and releases thus more neurotransmitters. 46 23
Graded versus Action Potentials 47 24