RT Journal Article
SR Electronic
T1 The β<sub>2a</sub> Subunit Is a Molecular Groom for the Ca<sup>2+</sup> Channel Inactivation Gate
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9046
OP 9052
DO 10.1523/JNEUROSCI.20-24-09046.2000
VO 20
IS 24
A1 Restituito, S.
A1 Cens, T.
A1 Barrere, C.
A1 Geib, S.
A1 Galas, S.
A1 De Waard, M.
A1 Charnet, P.
YR 2000
UL http://www.jneurosci.org/content/20/24/9046.abstract
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.