Forskolin's structural analogue 1,9-dideoxyforskolin has Ca2+ channel blocker-like action in rat cerebellar granule cells.
Forskolin, routinely used as a specific activator of the cAMP pathway, is also a blocker of various ionic channels in a cAMP-independent way. We investigated, in rat cerebellar granule cells in culture, the effects of forskolin and its structural analogue 1,9-dideoxyforskolin on Ca2+ entry. Changes in cytosolic free Ca2+ concentration ([Ca]i) were monitored using fura-2 microfluorimetry. The increase in [Ca]i observed in response to membrane depolarization by 30 mM KCI was reduced by 20% in the presence of 100 microM forskolin, and by 71% with the same concentration of 1,9-dideoxyforskolin. A dose-response curve for 1,9-dideoxyforskolin gave an estimated IC50 of 54 microM. Additional experiments using the patch-clamp technique showed that 100 microM 1,9-dideoxyforskolin inhibit voltage-activated Ca2+ currents by 63%, although forskolin had no significant effect in the same conditions. This blocking effect of 1,9-dideoxyforskolin is not specific of a given Ca2+ channel type.
Zerr
P
P
Laboratoire de Neurobiologie Cellulaire (UPR 9009 CNRS), Strasbourg, France.
Becherer
U
U
Rodeau
J L
JL
Feltz
A
A
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism*; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats
D002121:Calcium Channel Blockers; D005576:Colforsin; D001464:Barium; C047983:1,9-dideoxyforskolin; D002118:Calcium; D016257:Fura-2