Cardiac myocyte volume, Ca2+ fluxes, and sarcoplasmic reticulum loading in pressure-overload hypertrophy

Leanne M D Delbridge, Hiroshi Satoh, Weilong Yuan, Jose W M Bassani, Ming Qi, Kenneth S Ginsburg, Allen M. Samarel, Donald M Bers

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Alterations in cellular Ca2+ transport and excitation-contraction coupling may contribute to dysfunction in cardiac hypertrophy. Left ventricular myocytes were isolated from rat hearts after 15-18 wk of suprarenal abdominal aortic banding to evaluate the hypothesis that hypertrophy alters the relationship between Ca2+ current (I(Ca)) and sarcoplasmic reticulum (SR) Ca2+ load during steady-state voltage-clamp depolarization. Mean arterial pressure (MAP) and heart weight-to-body weight ratio of banded (B) animals were significantly higher than in control or sham-operated animals (C). Isolated myocyte dimensions and volume increased in parallel with whole heart hypertrophy and elevation in MAP. However, the relationship between membrane surface area (measured by capacitance) and cell volume (measured by laser scanning confocal microscopy) was unaltered (C: 8.9 ± 0.3; B: 8.5 ± 0.4 pF/pl). No differences in the voltage dependence of I(Ca) activation, steady-state inactivation, or recovery from inactivation were detected between C and B myocytes. Maximal (I(Ca)) density for the two groups was also not different either under basal conditions (C: 4.28 ± 0.98; B: 4.57 ± 0.60 pA/pF) or in the presence of 1 μM isoproterenol (C: 16.6 ± 2.3; B: 16.5 ± 2.3 pA/pF). The fraction of Ca2+ released from the SR by a single twitch was 55.4 ± 9.4% in C and 37.1 ± 6.9% in B (not significantly different). Steady-state Ca2+ influx during a twitch was calculated in units of micromoles per liter of nonmitochondrial volume from the integral of I(Ca) (C: 13.4 ± 0.7 μM; B: 13.3 ± 0.8 μM). The SR Ca2+ load was similarly calculated by integration of Na+/Ca2+ exchange current induced by rapid caffeine application (C: 140 ± 9 μM; B: 169 ± 18 μM). 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume272
Issue number5 41-5
StatePublished - 1997
Externally publishedYes

Keywords

  • calcium current
  • laser scanning confocal microscopy
  • sodium/calcium exchange current

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Delbridge, L. M. D., Satoh, H., Yuan, W., Bassani, J. W. M., Qi, M., Ginsburg, K. S., Samarel, A. M., & Bers, D. M. (1997). Cardiac myocyte volume, Ca2+ fluxes, and sarcoplasmic reticulum loading in pressure-overload hypertrophy. American Journal of Physiology - Heart and Circulatory Physiology, 272(5 41-5).