PT  - JOURNAL ARTICLE
AU  - Restituito, S.
AU  - Cens, T.
AU  - Barrere, C.
AU  - Geib, S.
AU  - Galas, S.
AU  - De Waard, M.
AU  - Charnet, P.
TI  - The β<sub>2a</sub> Subunit Is a Molecular Groom for the Ca<sup>2+</sup> Channel Inactivation Gate
AID  - 10.1523/JNEUROSCI.20-24-09046.2000
DP  - 2000 Dec 15
TA  - The Journal of Neuroscience
PG  - 9046--9052
VI  - 20
IP  - 24
4099  - http://www.jneurosci.org/content/20/24/9046.short
4100  - http://www.jneurosci.org/content/20/24/9046.full
SO  - J. Neurosci.2000 Dec 15; 20
AB  - 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.