The β2a Subunit Is a Molecular Groom for the Ca2+ Channel Inactivation Gate

By S. Restituito, T. Cens, C. Barrère, S. Geib, S. Galas, M. Waard, P. Charnet. Journal of Neuroscience, 2000

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Ca2+ channel inactivation is a key element in controlling the level of Ca2+ entry through voltage-gated Ca2+ channels. Interaction between the pore-forming α1 subunit and the auxiliary β subunit is known to be a strong modulator of voltage-dependent inactivation. Here, we demonstrate that an N-terminal membrane anchoring site (MAS) of the β2a subunit strongly reduces α1A(CaV2.1) Ca2+ channel inactivation. This effect can be mimicked by the addition of a transmembrane segment to the N terminus of the β2a subunit. Inhibition of inactivation by β2a also requires a link between MAS and another important molecular determinant, the β interaction domain (BID). Our data suggest that mobility of the Ca2+channel I–II loop is necessary for channel inactivation. Interaction of this loop with other identified intracellular channel domains may constitute the basis of voltage-dependent inactivation. We thus propose a conceptually novel mechanism for slowing of inactivation by the β2a subunit, in which the immobilization of the channel inactivation gate occurs by means of MAS and BID.

Subfields: Cardiology and Cardiovascular Medicine, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7e649229c68c0521d358e46ade0635a6064fee4c