Phospholamban deficiency alters inactivation kinetics of l-type
ca2+ channels in mouse ventricular myocytes.
Masaki, Hiroya, Yoji Sato, Wusheng Luo, Evangelia G. Kranias, and
Atsuko Yatani.
Department of Pharmacology and Cell Biophysics, University of
Cincinnati College of Medicine, Cincinnati, Ohio 45267
APStracts 3:0341H, 1996.
Entry of Ca2+ through voltage-dependent L-type Ca2+ channel (CaCh) is
critical for contraction in cardiac cells. In recent studies, cells
from the PLB knockout (PLB-KO) mouse hearts showed significantly
increased basal contractility with enhanced sarcoplasmic reticulum
(SR) Ca2+-uptake. To test whether these effects of PLB ablation were
associated with alterations of CaCh function, we compared the
properties of Ca2+ channel currents (ICa) in ventricular myocytes
isolated from wild-type (WT) and PLB-KO mouse hearts. CaCh from mouse
myocytes exhibited voltage-dependent gating and sensitivity to
dihydropyridine drugs, similar to other mammalian species, and these
properties were not altered by PLB ablation. ICa from both WT and
PLB-KO cells revealed two (fast and slow) components of inactivation
kinetics. However, the proportion of the faster component was
significantly larger in PLB-KO cells. Ryanodine (10 mM) reduced the
rate of inactivation of ICa for both WT and PLB-KO cells, but the
reduction was more prominent in PLB-KO cells compared with WT cells.
In contrast, the inactivation in Ba2+ solution could be fitted by a
single exponential similar to the slower component in Ca2+, and this
was not altered in PLB-KO cells. The increase in the fast Ca2+
-dependent inactivation component in PLB-KO cells supports the
hypothesis that Ca2+ released from the SR regulates Ca2+ channel
inactivation by affecting the levels of Ca2+ near the channel and
suggests that this may be an important compensatory mechanism in the
hyperdynamic PLB-KO heart.
Received 26 July 1996; accepted in final form 4 August 1996.
APS Manuscript Number H673-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996