Mechanisms underlying enhanced cardiac excitation contraction coupling observed in the senescent sheep myocardium

Ageing related stiffening of the vascular system is believed to be in part responsible for a number of clinical outcomes including hypertension and heart failure. In the present study, we sought to determine whether there are alterations in cardiac excitation contraction coupling that may help compensate for the increased vessel stiffness. Experiments were performed on single cardiac myocytes isolated from young (18 months) and aged (>8 years) sheep. Intracellular Ca2+ concentration, action potentials, L-type Ca2+ currents and SR Ca2+ content were measured at 23 °C. With ageing, cell capacitance increased by 26% indicating cellular hypertrophy. Action potential duration (APD90) (590 ± 21 vs. 726 ± 36 ms), Ca2+ transient amplitude (112 ± 15 vs. 202 ± 25 nmol l–1) and fractional cell shortening (by 37%) also increased in the aged hearts (all values P < 0.05). The larger Ca2+ transient amplitude observed under current clamp conditions was maintained under voltage clamp control; however, SR Ca2+ content was identical. Both the peak L-type Ca2+ current (2.8 ± 0.3 vs. 4.9 ± 0.5 pA pF–1) and integrated Ca2+ entry (5.1 ± 0.7 vs. 7.9 ± 0.8 μmol l–1, all P < 0.01) were greater in aged cells. In this study we show that in the ageing ovine myocardium, the amplitude of the systolic Ca2+ transient is increased. The larger Ca2+ transients cannot simply be explained by changes in APD and we suggest that the greater inward L-type Ca2+ current provides a more effective trigger for calcium-induced-calcium release from the SR whilst maintaining a stable SR Ca2+ content. These changes in cardiac excitation contraction coupling may help maintain cardiac output in the face of increased great vessel stiffness.