DISTINCTIVE FUNCTIONAL-PROPERTIES OF THE NEURONAL BII (CLASS-E) CALCIUM-CHANNEL

Functional diversity of voltage-dependent calcium channels (VDCC) is p rimarily due to the existence of six distinct genes of the channel-for ming subunit alpha(1), which can be further classified into the L-type and neuronal non-L-type subfamilies. We have examined functional prop erties of the calcium channel BII expressed from the cloned cDNA, in X enopus oocytes, and compared the results with the other members of the non-L-type subfamily, the BI and BIII channels. The BII channel is a high voltage-activated calcium channel pharmacologically featured by i ts unique sensitivity to the inorganic blocker Ni2+. The decaying comp onent of the BII current shows high sensitivity to Ni2+ similar to tha t of the low voltage-activated channels and the R-type channel in cere bellar granule cells, whereas the sustained component is relatively re sistant to Ni2+ as are the other high voltage-activated calcium channe ls. Dihydropyridines, omega-CgTx-GVIA, and omega-Aga-IVA, which have b een used to discriminate L-, N-, and P-types, do not affect the BII cu rrent. The mode of modulation of the BII channel by auxiliary subunits is strikingly different from that observed in the L-type channels. Bo th activation and inactivation rates of the BII current are decelerate d by coexpression of the beta subunit, and this effect is cancelled by further coexpression of the alpha(2) subunit. In situ tissue distribu tion studies indicate a higher level of BII mRNA expression in the hip pocamus compared to other brain regions, revealing important differenc e in the relative abundance of BI, BII, and BIII channels in brain tis sues. Overall, the results suggest that the BII channel forms a novel functional category of VDCC that is different from T-, L-, N-, and P-t ype.