FUNCTIONAL EXPRESSION OF A RAPIDLY INACTIVATING NEURONAL CALCIUM-CHANNEL

DIVERSE types of calcium channels in vertebrate neurons are important in linking electrical activity to transmitter release, gene expression and modulation of membrane excitability1. Four classes of Ca2+ channe ls (T, N, L and P-type) have been distinguished2-6 on the basis of the ir electrophysiological and pharmacological properties. Most of the re cently cloned Ca2+ channels7-16 fit within this functional classificat ion. But one major branch of the Ca2+ channel gene family, including B II (ref. 15) and doe-1 (ref. 16), has not been functionally characteri zed. We report here the expression of doe-1 and show that it is a high -voltage-activated (HVA) Ca2+ channel that inactivates more rapidly th an previously expressed calcium channels. Unlike L-type or P-type chan nels, doe-1 is not blocked by dihydropyridine antagonists or the pepti de toxin omega-Aga-IVA, respectively. In contrast to a previously clon ed N-type channel14, doe-I block by omega-CTx-GVIA requires micromolar toxin and is readily reversible. Unlike most HVA channels, doe-1 also shows unusual sensitivity to block by Ni2+. Thus, doe-1 is an HVA Ca2 + channel with novel functional properties. We have identified a Ca2channel current in rat cerebellar granule neurons that resembles doe-1 in many kinetic and pharmacological features.