Activators of adenylate cyclase and cyclic AMP prolong calcium-dependent action potentials of mouse sensory neurons in culture by reducing a voltage-dependent potassium conductance.
The effects of compounds that activate adenylate cyclase and of cAMP on calcium-dependent action potentials recorded from mouse dorsal root ganglion neurons were assessed. Application of compounds that stimulate the adenylate cyclase system (forskolin, cholera toxin, and prostaglandin E1) increased action potential duration with an associated decrease in afterhyperpolarization. An adenylate cyclase inhibitor, 2',5'-dideoxyadenosine, partially inhibited the responses to forskolin and cholera toxin. cAMP analogs mimicked the effect of forskolin, and the phosphodiesterase inhibitor theophylline enhanced the response to forskolin. Following intracellular injection of the potassium channel blocker cesium, the forskolin response was reduced. Forskolin did not significantly alter resting membrane potential or conductance. The action potential responses to forskolin were voltage dependent, being reduced when the membrane was held at less negative (less than -50 mV) potentials. The data suggest that activators of adenylate cyclase and cAMP prolong calcium-dependent action potentials by blocking a voltage-dependent potassium conductance that is responsible, in part, for action potential repolarization and that inactivates at membrane potentials less negative than -50 mV.
D000200:Action Potentials / Q000187:drug effects; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D004553:Electric Conductivity; D004789:Enzyme Activation; D051379:Mice; D009475:Neurons, Afferent / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D011930:Reaction Time; D013806:Theophylline / Q000494:pharmacology
D003839:Deoxyadenosines; D005576:Colforsin; D002586:Cesium; D016048:Dideoxyadenosine; D002772:Cholera Toxin; C021008:2',5'-dideoxyadenosine; D013806:Theophylline; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000527:Alprostadil; D011188:Potassium; D002118:Calcium