Essential Ca2+-Binding Motif for Ca2+-Sensitive Inactivation of L-Type Ca2+ Channels

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Science  01 Dec 1995:
Vol. 270, Issue 5241, pp. 1502-1506
DOI: 10.1126/science.270.5241.1502


Intracellular calcium (Ca2+) inhibits the opening of L-type (α1C) Ca2+ channels, providing physiological control of Ca2+ entry into a wide variety of cells. A structural determinant of this Ca2+-sensitive inactivation was revealed by chimeric Ca2+ channels derived from parental α1C and α1E channels, the latter of which is a neuronal channel lacking Ca2+ inactivation. A consensus Ca2+-binding motif (an EF hand), located on the α1C subunit, was required for Ca2+ inactivation. Donation of the α1C EF-hand region to the α1E channel conferred the Ca2+-inactivating phenotype. These results strongly suggest that Ca2+ binding to the α1C subunit initiates Ca2+ inactivation.