where R = 8.314 J/(molK) is the gas constant, T is absolute temperature, zn is the valence of ion n, F = 9.648 x 104 C/mol and is Faraday's constant, [Xn]° is the outer concentration of ion n, and [XJ1 is the inner concentration of ion n. Intuitively, the equilibrium potential is the value of membrane potential at which ionic fluxes due to concentration gradients and voltage gradients cancel one another, leading to zero net flux of the ion. Note that ionic

current, as defined, is positive for outward flux of a positive ion. For neurons, [Na+]o>[Na + ]'; consequently, VNa typically ranges from 40 to 50 mV and 1Na<0. In contrast, [K + ]'>[K + ]°; VK ranges from -70 to — 100mV and 1K>0. The fact that resting membrane potential is far from VNa and close but typically not equal to VK implies that these ions are out of equilibrium, and thus that there is a constant trickle of each, even at rest. This flux is opposed by energy-expending ionic pumps, most notably the Na + /K + ATPase, which serve to maintain Na+ and K + concentration gradients and, consequently, equilibrium potentials.

Among the first quantitative clues regarding the mechanisms underlying the action potential came from ionic substitution experiments demonstrating that Na+ and K+ are the primary ions responsible for the phenomenon. Other early experiments demonstrated that membrane conductance, but not membrane capacitance, changes during the course of the action potential. Together, these results suggested the hypothesis that fluxes of Na+ and K + , driven by changes in ion-specific conductances, are responsible for the action potential. It is important to note that changes in membrane potential are not induced by changes in intracellular concentrations of Na+ and K + : Ionic fluxes during individual action potentials are small enough that concentrations remain essentially unper turbed. Instead, ionic fluxes alter Vm by changing the distribution of charge very near the membrane.

B. The Hodgkin-Huxley Model of the Space-Clamped Action Potential

Researchers in the middle of the 20th century hypothesized that the Na+ and K+ conductances underlying the action potential are "gated" (i.e., turned on and off) by changes in membrane potential. To test this hypothesis, they devised methods to measure ionic fluxes while controlling membrane potential Vm at a fixed value throughout the length of the axon. The process of controlling Vm, called voltage clamping, simplifies the behavior of the hypothesized voltage-dependent "gates." The process of making Vm the same throughout the axon, called space clamping, prevents complex spatial spread of excitation. Under these conditions, Na+ and K+ fluxes can be isolated either by manipulation of ionic concentrations (and thus equilibrium potentials) or by using specific blockers of particular conductances. (Tetrodotoxin is the classic blocker of Na+ conductances; tetraethyl ammonium blocks many K+ conductances.) Isolated Na + and K + fluxes from simulations are shown in Fig. 3 for many values of membrane potential. As hypothesized, these fluxes are voltage dependent. Na+ and a

Aspergers Answers Revealed

Aspergers Answers Revealed

Learn How to Help, Understand amp Cope with your Aspergers Child from a UK Chartered Educational Psychologist. Before beginning any practice relating to Aspergers it is highly recommended that you first obtain the consent and advice of a qualified health,education or social care professional.

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