CLONING AND FUNCTIONAL EXPRESSION OF A VOLTAGE-GATED CALCIUM-CHANNEL ALPHA(1) SUBUNIT FROM JELLYFISH

Voltage-gated Ca2+ channels in vertebrates comprise at least seven mol ecular subtypes, each of which produces a current with distinct kineti cs and pharmacology. Although several invertebrate Ca2+ channel cu, su bunits have also been cloned, their functional characteristics remain unclear, as heterologous expression of a full-length invertebrate chan nel has not previously been reported. We have cloned a cDNA encoding t he cu, subunit of a voltage-gated Ca2+ channel from the scyphozoan jel lyfish Cyanea capillata, one of the earliest existing organisms to pos sess neural and muscle tissue. The deduced amino acid sequence of this subunit, named CyCa alpha(1), is more similar to vertebrate L-type ch annels (alpha(1S), alpha(1C), and alpha(1D)) than to non-1-type channe ls (alpha(1A), alpha(1B), and alpha(1E)) or low voltage-activated chan nels (alpha(1G)) Expression of CyCa alpha(1) in Xenopus oocytes produc es a high voltage-activated Ca2+ current that, unlike vertebrate L-typ e currents, is only weakly sensitive to 1,4-dihydropyridine or phenyla lkylamine Ca2+ channel blockers and is not potentiated by the agonist S(-)-BayK: 8644. In addition, the channel is less permeable to Ba2+ th an to Ca2+ and is more permeable to Sr2+. CyCa alpha(1) thus represent s an ancestral L-type alpha(1) subunit with significant functional dif ferences from mammalian L-type channels.