Forskolin prolongs action potential duration and blocks potassium current in embryonic chick sensory neurons.
To determine if alterations in internal cyclic adenosine monophosphate (cAMP) play a role in modulation of voltage-dependent channels in embryonic chick sensory neurons in vitro, forskolin (a direct activator of adenylate cyclase) was tested on the cells. Forskolin, in concentrations between 1 and 100 microM, produced dose-dependent, reversible increases in action potential duration. This effect of forskolin was blocked by incubation of the neurons in 1 mM 2',5'-dideoxyadenosine, an inhibitor of forskolin-induced activation of cyclase in other cells. This suggests that the increase in action potential duration is likely to be mediated by activation of adenylate cyclase. Cholera toxin, another cyclase activator, also increased action potential duration when applied to the sensory neurons in a concentration of 10 micrograms/ml. Forskolin applied to voltage-clamped neurons decreased a voltage-dependent outward current, a result consistent with its effect on the action potential. These effects of forskolin are mimicked by capsaicin, but are in marked contrast to those previously reported for norepinephrine on the action potential and membrane currents (Dunlap and Fischbach 1981). Furthermore, forskolin does not block (or attenuate) the effects of norepinephrine, suggesting that increases in adenylate cyclase activity are most likely not involved in norepinephrine's action on the calcium channel.
Dunlap
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002642:Chick Embryo; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011930:Reaction Time
D004224:Diterpenes; D007473:Ion Channels; D005576:Colforsin; D000242:Cyclic AMP; D011188:Potassium; D002211:Capsaicin; D009638:Norepinephrine