Activation of adenylate cyclase by forskolin prolongs calcium action potential duration in lamprey sensory neurons

Abstract

Calcium-dependent action potentials of primary sensory neurons in the isolated spinal cord of the lamprey were greatly prolonged in duration by forskolin, an activator of adenylate cyclase in other systems. This effect was dose-dependent over the tested range of 25–400 μM with an EC 50 of 55 μM. Experiments were performed to establish a role for adenylate cyclase and adenosine 3′,5′-cyclic monophosphate (cAMP) as mediators of the forskolin effect. The prolonging action of forskolin on the Ca action potential was significantly reduced in the presence of the adenylate cyclase inhibitor 2′,5′-dideoxyadenosine. The inactive forskolin analogue 1,9-dideoxyforskolin did not prolong the duration of the Ca action potential, while forskolin treatment of the same cells produced a large and rapid increase in action potential duration. In addition, the prolonging action of forskolin was potentiated by the phosphodiesterase inhibitor, theophylline. It is concluded that forskolin acts in lamprey sensory neurons to activate adenylate cyclase and raise intracellular cAMP levels which in turn mediate the increase in Ca action potential duration.