Intro to Pharmacology and Toxicology
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Ion channels give rise to action potentials in excitatory cells. Other cells use ions for regulation. The action potential is due to an unequal distribution of charges in each side of the plasma membrane, and to the differential permeability of the membrane to different ions. All cells have a membrane potential between -40 mV and -100 mV, which can be measured by one electrode inside and another outside the cell.
When the inside of the cells is more negative than normal, it is hyperpolarized. When the inside of the cell is more positive than normal, it is depolarized. Inward currents are negative or shown as downward trends in a graph, while outward currents are positive or shown as upward trends in a graph. The mean current for an ion depends on the number of channels (N), the current of a single channel (i) and the probability of a channel being open (P):
Imean = NPi
Action potentials reach a maximum, which is constant for a given cells type. They travel at a constant velocity and have a constant amplitude. This was not well known until the late 1940s when Hodgkin and Kats determined the role of Na+ in the action potential. Early work was done in squid axons which are very large (1-2 mm in diameter). Later the voltage clamp was developed to keep voltage constant and measure current using a feedback amplifier.
When cells hyperpolarize, membrane permeability does not change. When cells depolarize there is an inward current that turns into an outward current. Assuming that each ion flows down its concentration gradient, the Nernst equation calculates the membrane potential for each ion:
Eion = RT log [ion]out
zF [ion]in
where Eion is the equilibrium potential for an ion across the membrane, R is the gas constant, T is the absolute temperature, z the ion valence and F the Faraday constant (at 20ºC, RT/F = 58). For example, under standard conditions:
ENa+ = 58 mV • log
145 mM = 67 mV
1
12 mM
(this is straight from my notes but does not make sense to
me, not sure what I'm missing)
If the current is larger than the Na+ potential, (i > ENa+), Na+ will flow out of the cell. If the current is lower than the Na+ potential (i < ENa+), Na+ will flow into the cell (??). Conductance is the inverse of resistance and in cells is the same as membrane permeability. In cells, the conductance of Na+ changes rapidly and returns to normal quickly. K+ conductance changes after Na+'s, more slowly, and the change lingers longer.
In
the animal kingdom, sodium channels are highly conserved, and so are action
potentials. The channel has four domains, each with six membrane spanning regions.
Region #4 has a positively charged area. K+ and Ca2+ channels have similar structures.
Four different K+ channel families have been cloned, which can be divided into
two types:
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Modulation" or take a quiz: [Q1] [Q2] [Q3] [Q4].
Back to Basics: Action Potential (Physiology)
Check out a nice web page about the voltage-gated Na+ channel, includes animations.
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