Reduction of voltage-activated K+ currents by forskolin is not mediated via cAMP in pleural sensory neurons of Aplysia.
1. Forskolin is often used to activate adenylate cyclase in studies relating adenosine 3',5'-cyclic monophosphate (cAMP) to the modulation of membrane current. There is growing concern, however, that some actions of forskolin are independent of cAMP. With the use of two-electrode voltage-clamp techniques, we compared the effects of analogues of cAMP to the effects of forskolin on K+ currents in somata of sensory neurons that were isolated from pleural ganglia of Aplysia californica. 2. Analogues of cAMP did not reduce the peak amplitude of either the transient K+ current (IA) or the voltage-dependent K+ current (IK.V). Analogues of cAMP did reduce the previously described cAMP-sensitive S K+ current (IK.S). In contrast, forskolin reduced the peak amplitude of both IA and IK.V. Furthermore, both IA and IK.V were reduced by 1,9-dideoxy-forskolin, a derivative of forskolin that does not activate adenylate cyclase. These results indicate that the effects of forskolin and 1,9-dideoxy-forskolin on IA and IK.V were not mediated via cAMP. 3. Bath application of a modified form of forskolin (7-deacetyl-6-[N-acetylglycyl]-forskolin), which has enhanced water solubility and activates adenylate cyclase, reduced IK.S, but did not alter either IA or IK.V. Thus it appears that certain derivatives of forskolin can be used to activate adenylate cyclase and avoid some of the nonspecific actions on membrane current that are associated with forskolin.
Baxter
D A
DA
Department of Neurobiology and Anatomy, University of Texas Medical School, Houston 77225.
Byrne
J H
JH
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001048:Aplysia / Q000502:physiology*; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005724:Ganglia / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D015221:Potassium Channels; D005576:Colforsin; D000242:Cyclic AMP; C047983:1,9-dideoxyforskolin; D004121:Dimethyl Sulfoxide