CARDIAC MYOCYTE VOLUME, CA2-RETICULUM LOADING IN PRESSURE-OVERLOAD HYPERTROPHY( FLUXES, AND SARCOPLASMIC)

Alterations in cellular Ca2+ transport and excitation-contraction coup ling may contribute to dysfunction in cardiac hypertrophy. Left ventri cular myocytes were isolated from rat hearts after 15-18 wk of suprare nal abdominal aortic banding to evaluate the hypothesis that hypertrop hy alters the relationship between Ca2+ current (I-ca) and sarcoplasmi c reticulum (SR) Ca2+ load during steady-state voltage-clamp depolariz ation. Mean arterial pressure (MAP) and heart weight-to-body weight ra tio of banded (B) animals were significantly higher than in control or sham-operated animals (C). Isolated myocyte dimensions and volume inc reased in parallel with whole heart hypertrophy and elevation in MAP. However, the relationship between membrane surface area (measured by c apacitance) and cell volume (measured by laser scanning confocal micro scopy) was unaltered (C: 8.9 +/- 0.3; B: 8.5 +/- 0.4 pF/pl). No differ ences in the voltage dependence of I-ca activation, steady-state inact ivation, or recovery from inactivation were detected between C and B m yocytes. Maximal I-ca density for the two groups was also not differen t either under basal conditions (C: 4.28 +/- 0.98; B: 4.57 +/- 0.60 pA /pF) or in the presence of 1 mu M isoproterenol (C: 16.6 +/- 2.3; B: 1 6.5 +/- 2.3 pA/pF). The fraction of Ca2+ released from the SR by a sin gle twitch was 55.4 +/- 9.4% in C and 37.1 +/- 6.9% in B (not signific antly different). Steady-state Ca2+ influx during a twitch was calcula ted in units of micromoles per liter of nonmitochondrial volume from t he integral of I-ca (C: 13.4 +/- 0.7 mu M; B: 13.3 +/- 0.8 mu M). The SR Ca2+ load was similarly calculated by integration of Na+/Ca2+ excha nge current induced by rapid caffeine application (C: 140 +/- 9 mu M; B: 169 +/- 18 mu M). We conclude that significant cellular hypertrophy is associated with proportional increases in sarcolemmal I-ca influx, SR Ca2+ loading, and the amount of SR Ca2+ released in this model of pressure overload.