Functional expression of a rapidly inactivating neuronal calcium channel

Abstract

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⁺ channels (T, N, L and P-type) have been distinguished^2–6on the basis of their electrophysiological and pharmacological properties. Most of the recently cloned Ca²⁺ channels^7–16 fit within this functional classification. But one major branch of the Ca²⁺ channel gene family, including BII (ref. 15) and doe-1 (ref. 16), has not been functionally characterized. We report here the expression of doe-1 and show that it is a high-voltage-activated (HVA) Ca²⁺ channel that inactivates more rapidly than previously expressed calcium channels. Unlike L-type or P-type channels, doe-1 is not blocked by dihydropyridine antagonists or the peptide toxin ω-Aga-IVA, respectively. In contrast to a previously cloned N-type channel¹⁴, doe-1 block by ω-CTx-GVIA requires microm-olar 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 Ca²⁺ channel current in rat cerebellar granule neurons that resembles doe-1 in many kinetic and pharmacological features.