Essential Ca 2+ -Binding Motif for Ca 2+ -Sensitive Inactivation of L-Type Ca 2+ Channels

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Abstract
Intracellular calcium (Ca 2+ ) inhibits the opening of L-type (α 1C ) Ca 2+ channels, providing physiological control of Ca 2+ entry into a wide variety of cells. A structural determinant of this Ca 2+ -sensitive inactivation was revealed by chimeric Ca 2+ channels derived from parental α 1C and α 1E channels, the latter of which is a neuronal channel lacking Ca 2+ inactivation. A consensus Ca 2+ -binding motif (an EF hand), located on the α 1C subunit, was required for Ca 2+ inactivation. Donation of the α 1C EF-hand region to the α 1E channel conferred the Ca 2+ -inactivating phenotype. These results strongly suggest that Ca 2+ binding to the α 1C subunit initiates Ca 2+ inactivation.