New molecular determinant for inactivation of the human L-type α(1C) Ca2+ channel

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

Research output: Contribution to journalArticle

Abstract

Molecular cloning of the human fibroblast Ca2+ channel pore-forming α(1C) subunit revealed (Soldatov, 1992. Proc. Natl. Acad. Sci. USA 89:4628-4632) 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 α(1C,77) human recombinant L-type Ca2+ channel with those of its mutated isoform α(1C,94) containing the A752T replacement. Comparative quantification of steady-state availability of the current carried by α(1C,94) and α(1C,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.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalJournal of Membrane Biology
Volume177
Issue number2
DOIs
StatePublished - Sep 15 2000
Externally publishedYes

Fingerprint

Mutation
HEK293 Cells
Molecular Cloning
Threonine
Alanine
Protein Isoforms
Fibroblasts
Cell Line

Keywords

  • Ca overloading
  • Calcium channel
  • Inactivation
  • Mutant

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Cite this

Soldatov, N. M., Zhenochin, S., AlBanna, B., Abernethy, D. R., & Morad, M. (2000). New molecular determinant for inactivation of the human L-type α(1C) Ca2+ channel. Journal of Membrane Biology, 177(2), 129-135. https://doi.org/10.1007/s002320001106

New molecular determinant for inactivation of the human L-type α(1C) Ca2+ channel. / Soldatov, N. M.; Zhenochin, S.; AlBanna, B.; Abernethy, D. R.; Morad, M.

In: Journal of Membrane Biology, Vol. 177, No. 2, 15.09.2000, p. 129-135.

Research output: Contribution to journalArticle

Soldatov, NM, Zhenochin, S, AlBanna, B, Abernethy, DR & Morad, M 2000, 'New molecular determinant for inactivation of the human L-type α(1C) Ca2+ channel', Journal of Membrane Biology, vol. 177, no. 2, pp. 129-135. https://doi.org/10.1007/s002320001106
Soldatov, N. M. ; Zhenochin, S. ; AlBanna, B. ; Abernethy, D. R. ; Morad, M. / New molecular determinant for inactivation of the human L-type α(1C) Ca2+ channel. In: Journal of Membrane Biology. 2000 ; Vol. 177, No. 2. pp. 129-135.
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