LOCALIZATION AND FUNCTIONAL-PROPERTIES OF A RAT-BRAIN-ALPHA(1A) CALCIUM-CHANNEL REFLECT SIMILARITIES TO NEURONAL Q-TYPE AND P-TYPE CHANNELS

Functional expression of the rat brain alpha(1A) Ca channel was obtained by nuclear injection of an expression plasmid into Xenopus oocytes. The alpha(1A) Ca current activated quickly, inactivated slowly, and showed a voltage dependence typical of high voltage-activated Ca channels. The alpha(1A) current was partially blocked (approximate to 23%) by omega-agatoxin IVA (200 nM) and substantially blocked by omega-conotoxin MVIIC (5 mu M blocked approximate to 70%). Bay K 8644 (10 mu M) or omega-conotoxin GVIA (1 mu M) had no significant effect on the alpha(1A) current. Coexpression with rat brain Ca channel beta subunits increased the alpha(1A) whole-cell current and shifted the current-voltage relation to more negative values. While the beta(1b) and beta(3) subunits caused a significant acceleration of the alpha(1A) inactivation kinetics, the beta(2a) subunit dramatically slowed the inactivation of the alpha(1A) current to that seen typically for P-type Ca currents. In situ localization with antisense deoxyoligonucleotide and RNA probes showed that alpha(1A) was widely distributed throughout the rat central nervous system, with moderate to high levels in the olfactory bulb, in the cerebral cortex, and in the CA fields and dentate gyrus of the hippocampus. In the cerebellum, prominent alpha(1A) expression was detected in Purkinje cells with some labeling also in granule cells. Overall, the results show that alpha(1A) channels are widely expressed and share some properties with both Q- and P-type channels.