Action potential/extracellular fluid

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  1. The absolute difference in electrical potential between extracellular and intracellular compartments is the resting potential
    1. at rest, neurons are polarized with the inside negative with a typical range of –50 to –90 mV
    2. depolarization is a reduction in resting potential from –70 to –60 mV
    3. at some point the potential difference force (the electrical force) will equal the diffusion pressure force (the chemical gradient) and net diffusion will cease. This is the electrochemical equilibrium
    4. at the resting potential the conductance of Na, Cl, and Ca is zero – only K contributes to resting potential
    5. equilibrium or resting potential can be calculated by Nernst equation
      1. E = rt/zf * ln Io/Ii
      2. Thus for K, E is negative because intracellular K is much greater than extracellular K (-85 mV)
      3. For Na, E is positive because the intracellular Na is much less than the extracellular Na (60 mV)
      4. For Ca, E is 250 mV; for Cl, E is –70 mV
      5. The Nernst equation only incorporates a single ion conduction; the Goldman equation incorporates all ionic conductances and is more accurate at predicting the membrane potential
      6. Increasing the extracellular concentration of K raises the resting potential but the threshold remains the same, thus the cells are more excitable
      7. Manipulating Na or Ca has little effect on excitability because their channels are largely closed at rest
        1. In general, effects from manipulating extracellular ion concentrations are only seen when the channels are open. Thus increasing the Na extracellular concentration with increase the action potential somewhat but not the resting potential
        2. Ca will not affect the resting potential or action potential since Ca is not involved in either but will alter transmitter release from the axon terminals which require Ca.
  2. Action potential is initiated and propogated by voltage-dependent Na channels
    1. Na channel opens when the membrane is depolarized to its activation threshold
    2. Voltage gated channels have 4 transmembrane subunits. Each subunit has 6 transmembrane domains. This helix of domains form a tube. When the amino acids of the domains sense a change in voltage they rotate and allow Na ions to move intracellular.
    3. As depolarization reaches equilibrium potential for Na, voltage gated Na channels close and voltage gated K channels open
      1. As repolarization begins, K ions flow out of the cell
    4. from the time the Na channel closes until repolarization reaches the cell’s resting potential (-70 mV) the cell is absolutely refractory; after repolarization reaches –70 mV and remains hyperpolarized for some time before again returning to –70 mV the cell is in a relative refractory state
    5. The speed of propagation of an AP down a nerve in an unmyelinated fiber is proportional to the square root of its axon diameter
    6. Adding myelin to a nerve allows it to perform saltatory conduction. The myelinated areas do not need voltage gated channels because the AP propagates past those myelinated areas on its own. Only at unmyelinated nodes of Ranvier can the ionic flow occur. Myelinated nerves can pass the action potential through capacitative (electron) current (electromagnetic waves that run at right angles to the flow of ions)
      1. Thus a myelinated fiber will conduct 12-120 m/sec while an unmyelinated fiber will conduct .2-2 m/sec
    7. Tetrodotoxin (from the puffer fish) blocks voltage gated Na channels
      1. Lidocaine, veratridine, and ciguatoxin (from grouper fish) also block voltage gated Na channels; symptoms: sensory phenomenon of temperature reversal, paresthesias, headache, fatigue
    8. Tetraethylammonium (TEA) applied to the inside of a membrane blocks voltage gated K channels
      1. 4-aminopyridine also blocks K channels and has been tried in MS patients as a means to overcome nerve conduction block
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