Voltage-sensitive adenylyl cyclase activity in cultured neurons. A calcium-independent phenomenon.
Catalytic subunits of mammalian adenylyl cyclases have been proposed to contain 12 transmembrane domains, a property shared with some voltage-sensitive ion channels. Here we report that adenylyl cyclase activity in cerebellar neurons is synergistically stimulated by depolarizing agents and beta-adrenergic receptor activation. This phenomenon is Ca(2+)-independent and not attributable to Ca(2+)-stimulated adenylyl cyclase activity. Cholera toxin and forskolin also synergistically stimulate adenylyl cyclase activity in combination with depolarizing agents. We hypothesize that conformational changes in the catalytic subunit of the enzymes caused by changes in the membrane potential may enhance stimulation of adenylyl cyclases by the guanylyl nucleotide stimulatory protein. This novel mechanism for regulation of adenylyl cyclases generates robust cAMP signals that may contribute to various neuromodulatory events including some forms of neuroplasticity.
Reddy
R
R
Department of Pharmacology, University of Washington, Seattle 98195, USA.
Smith
D
D
Wayman
G
G
Wu
Z
Z
Villacres
E C
EC
Storm
D R
DR
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015640:Ion Channel Gating; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014701:Veratridine / Q000494:pharmacology
D015220:Calcium Channels; D005576:Colforsin; D011189:Potassium Chloride; D014701:Veratridine; D002772:Cholera Toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D002118:Calcium