The Journal of Membrane Biology

, Volume 177, Issue 2, pp 129–135

New Molecular Determinant for Inactivation of the Human L-Type α1C Ca2+ Channel

  • N.M.  Soldatov
  • S.  Zhenochin
  • B.  AlBanna
  • D.R.  Abernethy
  • M.  Morad

DOI: 10.1007/s002320001106

Cite this article as:
Soldatov, N., Zhenochin, S., AlBanna, B. et al. J. Membrane Biol. (2000) 177: 129. doi:10.1007/s002320001106

Abstract.

Molecular cloning of the human fibroblast Ca2+ channel pore-forming α1C subunit revealed (Soldatov, 1992. Proc. Natl. Acad. Sci. USA89:4628-4632) a naturally occurring mutation g2254→ a that causes the replacement of the conservative alanine for threonine at the position 752 at the cytoplasmic end of transmembrane segment IIS6. Using stably transfected HEK293 cell lines, we have compared electrophysiological properties of the conventional α1C,77 human recombinant L-type Ca2+ channel with those of its mutated isoform α1C,94 containing the A752T replacement. Comparative quantification of steady-state availability of the current carried by α1C,94 and α1C,77 showed that A752T mutation prevented a large (≈25%) fraction of the current carried by Ca2+ or Ba2+ from fully inactivating. This mutation, however, did not appear to alter significantly the Ca2+-dependence and kinetics of decay of the inactivating fraction of the current or its voltage-dependence. The data suggests that Ala752 at the cytoplasmic end of IIS6 might serve as a molecular determinant of the Ca2+ channel inactivation, possibly regulating the voltage-dependence of its availability.

Key words: Calcium channel — Inactivation — Mutant — Ca2+ overloading 

Copyright information

© 2000 Springer-Verlag New York Inc.

Authors and Affiliations

  • N.M.  Soldatov
    • 1
  • S.  Zhenochin
    • 2
  • B.  AlBanna
    • 2
  • D.R.  Abernethy
    • 1
  • M.  Morad
    • 2
  1. 1.National Institute on Aging, NIH, Gerontology Research Center, Baltimore, MD 21224, USAUS
  2. 2.Georgetown University Medical Center, Department of Pharmacology, Washington, DC, USAUS

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