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 obtain ed by nuclear injection of an expression plasmid into Xenopus oocytes. The alpha(1A) Ca current activated quickly, inactivated slowly, and s howed a voltage dependence typical of high voltage-activated Ca channe ls. The alpha(1A) current was partially blocked (approximate to 23%) b y omega-agatoxin IVA (200 nM) and substantially blocked by omega-conot oxin MVIIC (5 mu M blocked approximate to 70%). Bay K 8644 (10 mu M) o r omega-conotoxin GVIA (1 mu M) had no significant effect on the alpha (1A) current. Coexpression with rat brain Ca channel beta subunits inc reased the alpha(1A) whole-cell current and shifted the current-voltag e relation to more negative values. While the beta(1b) and beta(3) sub units 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 probe s showed that alpha(1A) was widely distributed throughout the rat cent ral nervous system, with moderate to high levels in the olfactory bulb , in the cerebral cortex, and in the CA fields and dentate gyrus of th e hippocampus. In the cerebellum, prominent alpha(1A) expression was d etected in Purkinje cells with some labeling also in granule cells. Ov erall, the results show that alpha(1A) channels are widely expressed a nd share some properties with both Q- and P-type channels.