Affordable Access

Access to the full text

The voltage dependence of gating currents of the neuronal CAV3.3 channel is determined by the gating brake in the I–II loop

Authors
  • Karmažínová, Mária1
  • Baumgart, Joel P.2
  • Perez-Reyes, Edward3
  • Lacinová, Ľubica1
  • 1 Slovak Academy of Sciences, Institute of Molecular Physiology and Genetics, Centre of Excellence for Cardiovascular Research, Bratislava, Slovakia , Bratislava (Slovakia)
  • 2 Cornell University Weill Medical College, Department of Anesthesiology, New York, NY, 10065, USA , New York (United States)
  • 3 University of Virginia, Department of Pharmacology, Charlottesville, VA, 22908, USA , Charlottesville (United States)
Type
Published Article
Journal
Pflügers Archiv - European Journal of Physiology
Publisher
Springer-Verlag
Publication Date
Feb 23, 2011
Volume
461
Issue
4
Pages
461–468
Identifiers
DOI: 10.1007/s00424-011-0937-2
Source
Springer Nature
Keywords
License
Yellow

Abstract

Low-voltage-activated CaV3 Ca2+ channels have an activation threshold around −60 mV, which is lower than the activation threshold of other voltage-dependent calcium channels (VDCCs). The kinetics of their activation at membrane voltages just above the activation threshold is much slower than the activation kinetics of other VDCCs. It was demonstrated recently that the intracellular loop connecting repeats I and II of all three CaV3 channels contains a so-called gating brake. Disruption of this brake yields channels that activate at even more hyperpolarized potentials with significantly accelerated kinetics. We have compared gating of a wild-type CaV3.3 channel and a mutated ID12 channel, in which the putative gating brake at the proximal part of the I–II loop was removed. Voltage dependence of the gating current activation was shifted by 34.6 mV towards more hyperpolarized potentials in ID12 channel. ON-charge movement was significantly faster in the ID12 channel, while the kinetics of the off-charge was not altered by the mutation. We conclude that the putative gating brake in I–II loop hinders not only the opening of the conducting pore but also the activating movement of voltage-sensing S4 segments, stabilizing the channel in its closed state.

Report this publication

Statistics

Seen <100 times