| dc.description | Cardiac excitation contraction (EC) coupling is the process whereby the depolarization of the sarcolemma results in a transient increase in intracellular Ca2+ and ultimately cardiac contraction. Several studies have suggested that cardiac contractile function is altered with advancing age. In aged ventricular myocytes, contraction and Ca2+ transient amplitudes are reasonably well preserved at rest, but the effects of aging on L-type Ca2+ current (ICa-L) are unclear. Furthermore, the relationship between contraction and ICa-L in aging heart has not been examined. Therefore, the first objective of this study was to simultaneously measure amplitudes of contraction and ICa-L in voltage clamped young adult and aged murine ventricular myocytes at physiological temperatures to determine the effects of aging on EC coupling. Results showed that contraction amplitudes, ICa-L amplitudes and Ca2+ transient amplitudes were significantly reduced in aged myocytes paced at 2 Hz. However, the gain of CICR, which is the amount of calcium released from the sarcoplasmic reticulum (SR) per nA of ICa-L, was similar in young adult and aged myocytes. This suggests that the relationship between ICa-L and contraction was not altered in aged myocytes. The present study also found that SR Ca2+ stores were similar in young adult and aged myocytes. The second objective of this study was to characterize the relationship between ICa-L, SR Ca2+ release and contraction in TG4 myocytes at physiological temperatures. Results showed that contraction amplitudes were significantly greater in field-stimulated TG4 myocytes than in WT myocytes. However, contraction amplitudes were similar in voltage clamped WT and TG4 myocytes, despite a significant reduction in the magnitude of ICa-L in TG4 myocytes. Peak Ca2+ transient amplitudes also were similar in voltage clamped WT and TG4 myocytes. Since peak contraction and Ca 2+ transient amplitudes were maintained despite a reduction in I Ca-L, this suggests that the gain of CICR was increased in TG4 myocytes. Furthermore, SR Ca2+ stores were significantly increased in TG4 myocytes. Thus, it is possible that the increased gain of CICR in TG4 myocytes is attributable, in part, to increased SR Ca2+ load. Together, these results suggest that contraction amplitude is maintained in TG4 myocytes by an increase in the gain of CICR. (Abstract shortened by UMI.) | en_US |
