The Resting State Ion Gradients Pumps And Potentials

The electrical signals are carried by the movement of charged ions across the cell membrane. This makes use of the potential energy stored across the cell membrane in the form of ionic gradients. Concentration gradients for the principal ions across a typical nerve cell membrane are indicated in Fig. 2.1(a). The cell interior has a high concentration of K+ ions and a low concentration of Na+, Cl— and Ca2+ ions relative to the exterior.

The ionic gradients themselves are generated by ion 'pumps' (carriers) (Fig. 2.1(b)). Thus, the Na+/K+ exchange pump (Na+/K+ ATPase) in the outer membrane generates the primary Na+ and K+ gradients across the cell membrane. Other pumps (a Ca2+ ATPase and/or a Na+/Ca2+ exchange pump) generate a high concentration gradient for Ca2+ ions. These pumps consume energy (in the form of ATP). It has been estimated that about 40% of the oxygen consumption of the brain is used to drive the Na+/K+ exchange pump.

There is also an electrical gradient across the membrane. At rest, the normal value of this potential (£rest) in most nerve cells is around — 70 mV (inside — ve). In general, the ion pumps themselves are not directly responsible for this (though they can contribute, since they are not electroneutral). Instead, it is due primarily to the passive diffusion of K+ ions back out of the cell down the chemical concentration gradient previously set up by the Na+/K+ exchange pump, leaving a small +ve charge deficit on the inside of the membrane. However, if K+ were the only ion involved, then, from the K+ concentration gradient, the Nernst equation predicts that the membrane potential should be about -90 mV:

Neurotransmitters, Drugs and Brain Function. Edited by R. A. Webster ©2001 John Wiley & Sons Ltd

Figure 2.1 (a) Resting ionic gradients across a nerve cell membrane. Concentrations [ ] are in mM (except intracellular Ca2+, in ^M). Arrows show the direction of the electrochemical gradients for passive ionic movement. (b) Principal active ion pumps. (1): plasmalemmal Na+/K+ ATPase. (2) Ca2+ ATPases

Figure 2.1 (a) Resting ionic gradients across a nerve cell membrane. Concentrations [ ] are in mM (except intracellular Ca2+, in ^M). Arrows show the direction of the electrochemical gradients for passive ionic movement. (b) Principal active ion pumps. (1): plasmalemmal Na+/K+ ATPase. (2) Ca2+ ATPases

This is the equilibrium potential for K+ ions (EK), i.e. the potential at which the electrical gradient pulling K+ into the cell just balances the chemical concentration gradient forcing K+ out of the cell. The 20 mV difference between Erest and EK is usually explained by assuming that the membrane is also slightly permeant to some other ion with a more positive equilibrium potential, such as Na+. The membrane potential is then given by the Goldman-Hodgkin-Katz (GHK) or constant-field equation:

E = RT/zF ln{([K+]out + a[Na+U)/([K+]in + a[Na+]in)}

where a is the ratio of the permeability of Na+ ions to that of K+ ions (PNa/PK). The GHK equation then predicts a value of — 70 mV for Erest if the permeability of the membrane to Na+ ions is about 4% of that to K+ ions (PNa/PK = 0.04). However, it should be noted that, at this potential, although the fluxes of total cations in and out of the cell are equal, the cell will gradually accumulate Na+ and lose K+, which will have to be corrected by the Na/K exchange pump; since this involves energy expenditure, it is not a true equilibrium state. The GHK equation can be expanded to include terms for other ions, such as Cl_ ions, which can have a profound effect on the membrane potential under certain circumstances (e.g. during the activation of Cl_ channels by inhibitory neurotransmitters).

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