Molecular Determinants of Calcium-Dependent Inactivation in Cardiac L-Type Calcium Channels

• Published in: Biochemical and biophysical research communications Vol. 201; no. 3; pp. 1117 - 1123
• Main Authors: Zong, Z.Q., Zhou, J.Y., Tanabe, T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.06.1994
• Subjects: Calcium - pharmacology; Calcium - physiology; Calcium Channels - drug effects; Cell Line; Electric Conductivity; Humans; In Vitro Techniques; Ion Channel Gating - drug effects; Recombinant Proteins
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1994.1821

We investigated the nature and structural requirements for Ca 2+-dependent inactivation of cardiac L-type Ca 2+ channel. Investigation of subunit requirements indicates that the interaction of α 1 subunit with ancillary subunits, especially β subunit, is important for this property. Replacement of the putative cytoplasmic regions of the cardiac α 1 subunit with skeletal muscle counterparts eliminates Ca 2+-dependent inactivation, indicating that the site regulated by Ca 2+ resides in the cytoplasmic region of the α 1 subunit. Deletion of the carboxy-terminal region of the cardiac α 1 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 Ca 2+ selectivity of Ca 2+ channels also eliminates Ca 2+-dependent inactivation, suggesting the close link between the ion selectivity and Ca 2+-dependent inactivation.