Cyclic AMP-dependent regulation of P-type calcium channels expressed in Xenopus oocytes

Xenopus oocytes injected with rat cerebellum mRNA, express voltage-dependent calcium channels (VDCC). These were identified as P-type Ca²⁺ channels by their insensitivity to dihydropyridines and -conotoxin and by their blockade by Agelenopsis aperta venom (containing the funnel-web spider toxins: FTX and -Aga-IV-A). Coinjection of cerebellar mRNA and antisense oligonucleotide complementary to the dihydropyridine-resistant brain Ca²⁺ channel, named BI [Mori Y. et al. (1991) Nature 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 suggesting that these clones encode a P-type VDCC. The macroscopic Ca²⁺ channel 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 kinase A, since it could be antagonized by a peptidic inhibitor of this enzyme. Positive regulation of P-type VDCC could be of importance in Purkinje neurons and motor nerve terminals where this channel is predominant.