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

We investigated the nature and structural requirements for Ca2+-dependent inactivation of cardiac L-type Ca2+ channel. Investigation of subunit requirements indicates that the interaction of alpha(1) subunit with ancillary subunits, especially beta subunit, is important for this property. Replacement of the putative cytoplasmic regions of the cardiac alpha(1) subunit with skeletal muscle counterparts eliminates Ca2+-dependent inactivation, indicating that the site regulated by Ca2+ resides in the cytoplasmic region of the alpha(1) subunit. Deletion of the 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 that strongly reduces Ca2+ selectivity of Ca2+ channels also eliminates Ca2+-dependent inactivation, suggesting the close link between the ion selectivity and Ca2+-dependent inactivation. (C) 1994 Academic Press, Inc.