Functional expression of the rat brain alA Ca channel was obtained by nuclear injection of an expression plasmid into Xenopus oocytes. The alA Ca current activated quickly, inactivated slowly, and showed a voltage dependence typical of high voltage-activated Ca channels. The alA current was partially blocked (=23%) by w-agatoxin IVA (200 nM) and substantially blocked by a-conotoxin MVIIC (5 pM blocked "70%). Bay K 8644 (10 pM) or a-conotoxin GVIA (1 IM) had no significant effect on the alA current. Coexpression with rat brain Ca channel 13 subunits increased the alA whole-cell current and shifted the current-voltage relation to more negative values. While the f18b and (3 subunits caused a significant acceleration of the alA inactivation kinetics, the 82. subunit dramatically slowed the inactivation of the alA current to that seen typically for P-type Ca currents. In situ loaliztion with antisense deoxyoligonucleotide and RNA probes showed that alA 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 alA expression was detected in Purkuije cells with some labeling also in granule cells. Overall, the results show that aj channels are widely expressed and share some properties with both Qand P-type channels.

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Calcium entry into excitable cells through voltage‐gated calcium channels can be influenced by both the rate and pattern of action potentials. We report here that a cloned neuronal alpha 1C L‐type calcium channel can be facilitated by positive pre‐depolarization. Both calcium and barium were effective as charge carriers in eliciting voltage‐dependent facilitation. The induction of facilitation was shown to be independent of intracellular calcium levels, G‐protein interaction and the level of phosphatase activity. Facilitation was reduced by the injection of inhibitors of protein kinase A and required the coexpression of a calcium channel beta subunit. In contrast, three neuronal non‐L‐type calcium channels, alpha 1A, alpha 1B and alpha 1E, were not subject to voltage‐dependent facilitation when coexpressed with a beta subunit. The results indicate that the mechanism of neuronal L‐type calcium channel facilitation involves the interaction of alpha 1 and beta subunits and is dependent on protein kinase A activity. The selective voltage‐dependent modulation of L‐type calcium channels is likely to play an important role in neuronal physiology and plasticity.

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