title: Reduced calcium current density in single myocytes isolated from hypertrophied failing guinea pig hearts.
abstract: The present study explored the possibility that an alteration in the transmembrane calcium current (ICa), through its ability to modulate Ca2+ release from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca2+]i we previously observed in hypertrophied failing myocardium. Whole-cell patch clamp was used to measure ICa in single guinea pig ventricular myocytes isolated from hearts of normal guinea pigs and from guinea pig hearts in which hypertrophy and failure were induced by gradually developing left ventricular pressure overload subsequent to ascending aortic banding of young animals. Membrane capacitance (Cm) was significantly greater. and ICa, normalized for Cm, was significantly lower in myocytes from hypertrophied failing hearts. Myocytes from hypertrophied failing hearts did not differ significantly from normal myocytes in terms of the voltage-dependence of the activation variable (d) of ICa (except at -30 mV), the time course of removal of inactivation of ICa, and the time constant of decay of ICa. Measurement of the voltage dependence of the inactivation variable (f) of ICa showed that significantly more steady-state inactivation was present at 0, -10, and -20 mV in myocytes from hypertrophied failing hearts. Multiple regression analysis of all data indicated that ICa density decreased with increasing myocyte membrane area (as reflected by Cm) irrespective of any specific effects of hypertrophy and heart failure. We conclude that ICa, normalized for Cm, is significantly reduced in myocytes isolated from hypertrophied failing hearts, probably by a process associated with increased cell size, per se.
authors: Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
authors: Z
authors: Z
authors: Ming
authors: C
authors: C
authors: Nordin
authors: F
authors: F
authors: Siri
authors: R S
authors: RS
authors: Aronson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002469:Cell Separation; D005071:Evoked Potentials; D006168:Guinea Pigs; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D017136:Ion Transport; D008297:Male; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D015220:Calcium Channels; D002118:Calcium