Cellular distribution of calcium current is unaltered during compensated hypertrophy in the spontaneously hypertensive rat

Changes in cellular calcium (Ca2+) handling are thought to underlie the altered contraction that occurs during cardiac hypertrophy and failure. Recent work has highlighted the importance of t-tubules in the control of intracellular Ca2+. The present study was performed to investigate whether changes in the distribution of I-Ca between the surface and t-tubule membranes might contribute to the altered Ca2+ handling observed during compensated hypertrophy in the spontaneously hypertensive rat (SHR). Experiments were performed on ventricular myocytes isolated from 5-month-old SHR and normotensive Wistar-Kyoto (WKY) control rats. Osmotic shock using formamide was used to disrupt the t-tubular system and the whole-cell patch clamp technique used to monitor I (Ca) in the presence and absence of t-tubules. Membrane capacitance and I (Ca) were greater in control SHR than WKY myocytes; following detubulation, cell capacitance and I (Ca) both decreased and were no longer significantly different in the two cell types. The density of I-Ca was not significantly different in control SHR and WKY cells or in detubulated myocytes from the two species. These data suggest that the distribution of I-Ca is unchanged in SHR myocytes compared to WKY controls; I-Ca density in the t-tubules was 1.2-fold greater than in the sarcolemma in both strains. These data also imply that the increase in surface area in SHR myocytes is due principally to an increase in t-tubular area, which is accompanied by an approximately equivalent increase in I (Ca), so that the density of I-Ca at the cell surface and in the t-tubules remains the same. These changes would be expected to retain cell function and synchronicity of Ca2+ release in the SHR at this stage of compensated hypertrophy.