VIP INHIBITS N-TYPE CA2-INSENSITIVE BUT CHOLERA TOXIN-SENSITIVE PATHWAY( CHANNELS OF SYMPATHETIC NEURONS VIA A PERTUSSIS TOXIN)

The best characterized Ca2+ channel modulation in mam malian sympathet ic neurons is an inhibition of N-type channels via a pertussis toxin ( PTX)-sensitive heterotrimeric G protein. Here, we show that vasoactive intestinal polypeptide (VIP), an abundant neuropeptide in the PNS and CNS, inhibited N-type Ca2+ channels in rat sympathetic neurons in a v oltage-dependent, membrane-delimited manner. The effect of VIP was ins ensitive to PTX but was attenuated by cholera toxin or anti-G(s alpha) antibodies. VIP-mediated inhibition was independent of cAMP-dependent protein kinase A (PKA). The results provide evidence for a new signal transduction pathway in which N-type Ca2+ channel modulation requires activation of G(s alpha) but is independent of PKA-mediated phosphory lation.