The β2aSubunit Is a Molecular Groom for the Ca2+Channel Inactivation Gate

S. Restituito, T. Cens, C. Barrere, S. Geib, S. Galas, M. De Waard, P. Charnet
2000 Journal of Neuroscience  
Ca 2ϩ channel inactivation is a key element in controlling the level of Ca 2ϩ entry through voltage-gated Ca 2ϩ channels. Interaction between the pore-forming ␣ 1 subunit and the auxiliary ␤ 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 ␤ 2a subunit strongly reduces ␣ 1A (Ca V 2.1) Ca 2ϩ channel inactivation. This effect can be mimicked by the addition of a transmembrane segment to the N
more » ... e segment to the N terminus of the ␤ 2a subunit. Inhibition of inactivation by ␤ 2a also requires a link between MAS and another important molecular determinant, the ␤ interaction domain (BID). Our data suggest that mobility of the Ca 2ϩ 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 ␤ 2a subunit, in which the immobilization of the channel inactivation gate occurs by means of MAS and BID.
doi:10.1523/jneurosci.20-24-09046.2000 pmid:11124981 fatcat:vkhn7xihkngqzj3acwbbbu3cvu