Molecular determinants of calcium-dependent inactivation in cardiac L-type calcium channels.
We investigated the nature and structural requirements for Ca(2+)-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 Ca(2+)-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 alpha 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 Ca2+ selectivity of Ca2+ channels also eliminates Ca(2+)-dependent inactivation, suggesting the close link between the ion selectivity and Ca(2+)-dependent inactivation.
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06536-0812.
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Zong
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Zhou
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Tanabe
D002118:Calcium / Q000494:pharmacology* / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects*; D002460:Cell Line; D004553:Electric Conductivity; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D011994:Recombinant Proteins
D015220:Calcium Channels; D011994:Recombinant Proteins; D002118:Calcium