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Science 1 December 1995:
Vol. 270. no. 5241, pp. 1502 - 1506
DOI: 10.1126/science.270.5241.1502
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Reports

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

Marita de Leon,  Yan Wang,  Lisa Jones,  Edward Perez-Reyes,  Xiangyang Wei,  Tuck Wah Soong,  Terry P. Snutch,  David T. Yue (1)

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


M. de Leon, Y. Wang, L. Jones, D. T. Yue, Program in Molecular and Cellular Systems Physiology, Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
E. Perez-Reyes, Department of Physiology, Loyola University Chicago, 2160 South First Avenue, Maywood, IL 60153, USA.
X. Wei, Institute for Molecular Medicine and Genetics, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912, USA.
T. W. Soong and T. P. Snutch, Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
(1) To whom correspondence should be addressed.


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Determinants for Calmodulin Binding on Voltage-dependent Ca2+ Channels.
P. Pate, J. Mochca-Morales, Y. Wu, J.-Z. Zhang, G. G. Rodney, I. I. Serysheva, B. Y. Williams, M. E. Anderson, and S. L. Hamilton (2000)
J. Biol. Chem. 275, 39786-39792
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Interactions of Calmodulin with Two Peptides Derived from the C-terminal Cytoplasmic Domain of the Cav1.2 Ca2+ Channel Provide Evidence for a Molecular Switch Involved in Ca2+-induced Inactivation.
J. Mouton, A. Feltz, and Y. Maulet (2001)
J. Biol. Chem. 276, 22359-22367
   Abstract »    Full Text »    PDF »
Regulation of L-type Calcium Channels in Pituitary GH4C1 Cells by Depolarization.
R. Peri, D. J. Triggle, and S. Singh (2001)
J. Biol. Chem. 276, 31667-31673
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Molecular Basis of Calmodulin Tethering and Ca2+-dependent Inactivation of L-type Ca2+ Channels.
G. S. Pitt, R. D. Zuhlke, A. Hudmon, H. Schulman, H. Reuter, and R. W. Tsien (2001)
J. Biol. Chem. 276, 30794-30802
   Abstract »    Full Text »    PDF »
Calcium-induced Transitions between the Spontaneous Miniature Outward and the Transient Outward Currents in Retinal Amacrine Cells.
P. Mitra and M. M. Slaughter (2002)
J. Gen. Physiol. 119, 373-388
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On the Role of Ca2+- and Voltage-Dependent Inactivation in Cav1.2 Sensitivity for the Phenylalkylamine (-)Gallopamil.
S. Sokolov, E. Timin, and S. Hering (2001)
Circ. Res. 89, 700-708
   Abstract »    Full Text »    PDF »


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