Cellular metabolism regulating H and M currents in bullfrog sympathetic ganglia

Abstract

Much evidence has accumulated suggesting that neurons in autonomic and dorsal root ganglia possess voltage-dependent currents that link with transmitter receptors through intracellular signal transduction systems. The M current (IM), a voltage-dependent potassium current, was activated at potentials more positive than −65 mV, while the H current (IH), a voltage-dependent nonselective cationic current, was activated at potentials more negative than −50 mV. The hydrolyzable form of ATP was required to activate IM and IH. Intracellular application of calmodulin enhanced the amplitude of IM in a calcium-dependent manner. IM was reduced by W-7, a calmodulin antagonist, and by ML-9, an inhibitor of calmodulin-dependent protein kinase. IH was enhanced by intracellular loading with cyclic adenosine monophosphate (AMP) or bath application of forskolin and membrane-permeable cyclic AMP analogues. Isobutylmethylxanthine also increased the maximal conductance of IH. IH was depressed by H-8 but not by phorbol ester. It is concluded that the resting membrane conductance of these ganglion cells can be regulated by basal activities of calmodulin-dependent protein kinase and A kinase.Key words: peripheral neurons, M current, H current, calmodulin, adenylate cyclase.