The ionic basis of cell excitation

Excitable cells - nerve cells and the various types of muscle cells - have a prominent role in the physiological processes that are targeted by drug therapy. We will therefore spend some time looking at how electrical cell excitation works. 

The fundamental prerequisite of excitability is the presence of a membrane potential. A membrane potential is present in apparently all living cells. In non-excitable cells, the orientation of the membrane potential is always such that the cell interior is electrically negative against the outside. This orientation also prevails in excitable cells that are not currently excited, i.e. currently are at their resting potential. One fundamental function of this negative-inside membrane potential in all cells consists in powering active transport, usually in the form of sodiirm cotransport. 

Membrane potentials also exist across membranes within cells. An important example is the potential across the inner mitochondrial membrane, which is the major driving force of ATP synthesis. However, since the intracellular potentials don t have a prominent role in cell excitation and pharmacology, the following discussion will focus on the potentials that occur at the cytoplasmic membrane. 

All membrane potentials depend on the existence of ion gradients across the membrane in question. The major ion species that shape the form of both resting potentials and action potentials are K, Na, Ca, and Cf. The ion gradients result from the activities of three types of membrane proteins  

Ion pumps. These proteins use metabolic energy in the form of ATP to transport ions against their concentra- 

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These equations offer an adequate basis for the development of the negative membrane potential of 70 to 90 mV. Excitation as a process characterizing nerve and muscle cells is associated with a transient reduction or abolition of this membrane potential, and in some cases with a temporary "overshoot" or reversal of its polarity. Just as for the membrane potential, these major but transient perturbations in the production of action potentials have been adequately modeled in dynamics of ionic equilibria by Hodgkin and Huxley (2). 

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