CYCLIC AMP-DEPENDENT REGULATION OF P-TYPE CALCIUM CHANNELS EXPRESSED IN XENOPUS-OOCYTES

Xenopus oocytes injected with rat cerebellum mRNA, express voltage-dep endent calcium channels (VDCC). These were identified as P-type Ca2+ c hannels by their insensitivity to dihydropyridines and omega-conotoxin and by their blockade by Agelenopsis aperta venom (containing the fun nel-web spider toxins: FIX and omega-Aga-IV-A). Coinjection of cerebel lar mRNA and antisense oligonucleotide complementary to the dihydropyr idine-resistant brain Ca2+ channel, named BI [Mori Y. et al. (1991) Na ture 350:398-402] or rbA [Starr T. V. B. et al. (1991) Proc Natl Acad Sci USA 88: 5621-5625], strongly reduced the expressed Ba2+ current su ggesting that these clones encode a P-type VDCC. The macroscopic Ca2channel activity was increased by direct intraoocyte injection of cAMP . This increase in current amplitude was concomitant with a slowing of current inactivation, and was attributed to activation of protein kin ase A, since it could be antagonized by a peptidic inhibitor of this e nzyme. Positive regulation of P-type VDCC could be of importance in Pu rkinje neurons and motor nerve terminals where this channel is predomi nant.