[Relation between metabolism and the function of ion channels in the nerve cell membrane]

Abstract

The effect of varying intracellular 3.5-cAMP level on steady-state and voltage-dependent transmembrane ionic currents has been studied on both vertebrate and invertebrate nerve cells. A change in 3.5-cAMP level was achieved either by its direct introduction into the cell or by stimulation or inhibition of the activity of different enzymes of the cyclase system. Intracellular cAMP increase was found to activate a steady-state transmembrane current whose early component is related mainly to the increase of sodium and calcium conductance of the membrane, and a late one to increase of potassium conductance (possibly, activated by Ca2+ influx). The decrease of intracellular cAMP concentration (by intracellular dialysis) results in reduction of the potential-activated inward calcium current, whereas its increase restores the current. Restoration of calcium current can be achieved by activation of cellular adenylate cyclase, inhibition of phosphodiesterase or by direct intracellular introduction of the catalytic subunit of cAMP-dependent protein kinase. The evidence is presented that the observed regulatory effects are mediated through cAMP-dependent phosphorylation of proteins of corresponding ionic channels. The increase of intracellular Ca2+ level closely cooperates with this regulatory metabolic system by activation of a number of its enzymatic processes.