MOLECULAR DETERMINANTS OF CALCIUM-DEPENDENT INACTIVATION IN CARDIAC L-TYPE CALCIUM CHANNELS

We investigated the nature and structural requirements for Ca2+-depend ent inactivation of cardiac L-type Ca2+ channel. Investigation of subu nit requirements indicates that the interaction of alpha(1) subunit wi th ancillary subunits, especially beta subunit, is important for this property. Replacement of the putative cytoplasmic regions of the cardi ac alpha(1) subunit with skeletal muscle counterparts eliminates Ca2+- dependent inactivation, indicating that the site regulated by Ca2+ res ides in the cytoplasmic region of the alpha(1) subunit. Deletion of th e carboxy-terminal region of the cardiac al subunit does not eliminate this property, suggesting that the modulation by protein kinase A may not be involved in this mechanism. Single amino acid substitution tha t strongly reduces Ca2+ selectivity of Ca2+ channels also eliminates C a2+-dependent inactivation, suggesting the close link between the ion selectivity and Ca2+-dependent inactivation. (C) 1994 Academic Press, Inc.