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

作者：Marita de Leon, Yan Wang, Lisa P. Jones, Edward Perez‐Reyes, Xiangyang Wei, Tuck Wah Soong, Terry P. Snutch, David T. Yue · 发表于：Science · 年份：1995 · DOI：10.1126/science.270.5241.1502 · 被引用次数：282 · 研究领域：Ion channel regulation and function、Neuroscience and Neuropharmacology Research、Cardiac electrophysiology and arrhythmias

Intracellular calcium (Ca2+) inhibits the opening of L-type (alpha 1C) Ca2+ channels, providing physiological control of Ca2+ entry into a wide variety of cells. A structural determinant of this Ca(2+)-sensitive inactivation was revealed by chimeric Ca2+ channels derived from parental alpha 1C and alpha 1E channels, the latter of which is a neuronal channel lacking Ca2+ inactivation. A consensus Ca(2+)-binding motif (an EF hand), located on the alpha 1C subunit, was required for Ca2+ inactivation. Donation of the alpha 1C EF-hand region to the alpha 1E channel conferred the Ca(2+)-inactivating phenotype. These results strongly suggest that Ca2+ binding to the alpha 1C subunit initiates Ca2+ inactivation.