Enhanced Na⁺-Ca²⁺ exchange activity in cardiomyopathic Syrian hamster

The signaling of contraction by Ca²⁺ in the Syrian hamster (BIO 14.6) heart in the late stage of the cardiomyopathy (220 to 300 days old) was compared with that in age-matched healthy hamster hearts. Membrane current and cell shortening or intracellular Ca²⁺ transients were measured simultaneously in isolated whole-cell-clamped myocytes. The density of the L-type Ca²⁺ current was smaller in myopathic than in normal myocytes (2.13±0.3 versus 3.21±0.4 pA/pF at 0 mV, P<.05). In both control and myopathic myocytes, the L-type Ca²⁺ current gated the release of Ca²⁺ and activation of contraction. In myopathic myocytes, activation of contraction also activated a slowly inactivating inward current of 1.73±0.2 pA/pF. The Na⁺-Ca²⁺ exchanger generated this current (I_Na-Ca), because it was suppressed by rapid replacement of Na⁺ with Li⁺ and depletion of the intracellular Ca²⁺ pool by caffeine. I_Na-Ca, activated by rapid application of caffeine, was not significantly different in both groups (3.7±0.5 pA/pF in control hearts versus 3.9±0.5 pA/pF in cardiomyopathic hearts). The activation of the inward exchanger current in myopathic myocytes coincided with a significant prolongation of contraction and the intracellular Ca²⁺ transient and a delay in the onset of relaxation. These results suggest that the enhanced activity of the Na⁺-Ca²⁺ exchanger may be related to compromised sequestration of Ca²⁺ in these animals.