Inactivation of L-type calcium channels is determined by the length of the N terminus of mutant beta(1) subunits.

Details

Serval ID
serval:BIB_44AC15298CEB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inactivation of L-type calcium channels is determined by the length of the N terminus of mutant beta(1) subunits.
Journal
Pflügers Archiv
Author(s)
Jangsangthong Wanchana, Kuzmenkina Elza, Khan Ismail F.Y., Matthes Jan, Hullin Roger, Herzig Stefan
ISSN
1432-2013[electronic], 0031-6768[linking]
Publication state
Published
Issued date
2010
Volume
459
Number
3
Pages
399-411
Language
english
Abstract
Voltage-dependent calcium channel (Ca(v)) pores are modulated by cytosolic beta subunits. Four beta-subunit genes and their splice variants offer a wide structural array for tissue- or disease-specific biophysical gating phenotypes. For instance, the length of the N terminus of beta(2) subunits has major effects on activation and inactivation rates. We tested whether a similar mechanism principally operates in a beta(1) subunit. Wild-type beta(1a) subunit (N terminus length 60 aa) and its newly generated N-terminal deletion mutants (51, 27 and 18 aa) were examined within recombinant L-type calcium channel complexes (Ca(v)1.2 and alpha(2)delta2) in HEK293 cells at the whole-cell and single-channel level. Whole-cell currents were enhanced by co-transfection of the full-length beta(1a) subunit and by all truncated constructs. Voltage dependence of steady-state activation and inactivation did not depend on N terminus length, but inactivation rate was diminished by N terminus truncation. This was confirmed at the single-channel level, using ensemble average currents. Additionally, gating properties were estimated by Markov modeling. In confirmation of the descriptive analysis, inactivation rate, but none of the other transition rates, was reduced by shortening of the beta(1a) subunit N terminus. Our study shows that the length-dependent mechanism of modulating inactivation kinetics of beta(2) calcium channel subunits can be confirmed and extended to the beta(1) calcium channel subunit.
Keywords
Voltage-Dependent Calcium Channel, Whole-Cell Recording, Single Channel, Modeling, Channel Gating, Gated CA2+ Channels, Sodium-Channel, Single-Channel, Hypopp-1 Mutations, CA(V)1.2 Channel, Skeletal-Muscle, Gating Currents, Splice Variants, Amino-Terminus, Human Heart
Pubmed
Web of science
Create date
09/03/2010 11:55
Last modification date
20/08/2019 13:49
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