Complex modulation of L-type Ca2+ current inactivation by sorcin in isolated rabbit cardiomyocytes

Fowler, M. R., Colotti, G., Chiancone, E., Higuchi, Y., Seidler, T. and Smith, G. L. (2009) Complex modulation of L-type Ca2+ current inactivation by sorcin in isolated rabbit cardiomyocytes. Pflügers Archiv - European Journal of Physiology, 457(5), pp. 1049-1060. (doi:10.1007/s00424-008-0575-5)

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Publisher's URL: http://dx.doi.org/10.1007/s00424-008-0575-5

Abstract

Modulation of the L-type Ca2+ channel (LTCC) by sorcin was investigated by measuring the L-type Ca2+ current (I Ca,L) in isolated rabbit ventricular myocytes using ruptured patch, single electrode voltage clamp in the absence of extracellular Na+. Fifty millimolars EGTA (170 nM Ca2+) in the pipette solution buffered bulk cytoplasmic [Ca2+], but retained rapid Ca2+-dependant inactivation of I Ca,L,. Recombinant sorcin (3 μM) in the pipette significantly slowed time-dependant inactivation (τ fast: 8.8 ± 0.9 vs. 15.1 ± 1.7 ms). Sorcin had no significant effect on I Ca,L, after inhibition of the sarcoplasmic reticulum (SR). Using 10 mM 1,2-bis(o-N,N,N′,N′-tetraacetic acid (170 nM Ca2+), I Ca,L inactivation was then determined by a Ca2+ -independent, voltage-dependant process. Under these conditions, 3 μM sorcin speeded up inactivation. A similar effect was observed by substitution of Ca2+ with Ba2+. Down-regulation of endogenous sorcin to 27 ± 7% using an RNAi adenoviral vector slowed inactivation of I Ca,L by ∼42%. The effects of sorcin on voltage-dependant inactivation were mimicked by a truncated form of the protein containing only the Ca2+-binding domain. This data is consistent with two independent actions of sorcin on the LTCC: (1) slowing Ca2+-dependant inactivation and (2) stimulating voltage-dependant inactivation. The net effect of sorcin on the time-dependent inactivation of I Ca,L was a balance between these two effects. Under normal conditions, sorcin slows I Ca,L inactivation because the effects of Ca2+-dependant inactivation out-weigh the effects on voltage-dependant inactivation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Fowler, Dr Mark
Authors: Fowler, M. R., Colotti, G., Chiancone, E., Higuchi, Y., Seidler, T., and Smith, G. L.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Pflügers Archiv - European Journal of Physiology
Publisher:Springer-Verlag
ISSN:0031-6768
ISSN (Online):1432-2013
Published Online:02 September 2008

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