Essential Ca(2+)-binding motif for Ca(2+)-sensitive inactivation of L-type Ca2+ channels.
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.
D000595:Amino Acid Sequence; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D015854:Up-Regulation
D015220:Calcium Channels; D011993:Recombinant Fusion Proteins; D001464:Barium; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium