Cardiac-specific overexpression of G alpha q alters excitation-contractioncoupling in isolated cardiac myocytes

Citation
A. Yatani et al., Cardiac-specific overexpression of G alpha q alters excitation-contractioncoupling in isolated cardiac myocytes, J MOL CEL C, 31(7), 1999, pp. 1327-1336
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
ISSN journal
0022-2828 → ACNP
Volume
31
Issue
7
Year of publication
1999
Pages
1327 - 1336
Database
ISI
SICI code
0022-2828(199907)31:7<1327:COOGAQ>2.0.ZU;2-S
Abstract
Transgenic mice with cardiac-specific overexpression of G alpha q exhibit a biochemical and physiological phenotype of load-independent cardiac hypert rophy with contractile dysfunction. To elucidate the cellular basis for alt ered contractility, we measured cellular contraction, Ca2+ transients, and L-type Ca2+ channel currents (I-Ca) in left ventricular (LV) myocytes isola ted from non transgenic (NT) controls or G alpha q hearts. Although baselin e contractile function (% shortening) and the amplitude of Ca2+ transients in G alpha q myocytes were similar to NT myocytes, the rates of cellular sh ortening and relengthening and the duration of Ca2+ transients were prolong ed in G alpha q myocytes. Myocytes from G alpha q hearts had larger cell ca pacitance but no change in I-Ca density. voltage dependence of activation a nd inactivation. The responses of I-Ca to dihydropyridine drugs and a membr ane permeable cAMP analog, 8-(4-chlorophenylthio) cAMP, were not altered; h owever, the time course of I-Ca inactivation was significantly slower in G alpha q myocytes compared to NT myocytes, The kinetic difference in inactiv ation was abolished when Ba2+ was used as the charge carrier or when the sa rcoplasmic reticulum (SR) Ca2+ was depleted by ryanodine, suggesting that C a2+-dependent inactivation is reduced in G alpha q myocytes due to altered SR Ca2+ release. Consistent with this hypothesis, the function of SR as ass essed by the maximal Ca2+ uptake rates and the apparent affinity of SR Ca2-ATPase for Ca2+ was reduced in ventricles of G alpha q heart. These result s suggest that the reduced SR function contributes to the depressed contrac tility associated with this form of cardiac hypertrophy. (C) 1999 Academic Press.