The signaling of contraction by Ca2+ in the Syrian hamster (BIG 14.6)
heart in the late stage of the cardiomyopathy (220 to 300 days old) wa
s compared with that in age-matched healthy hamster hearts. Membrane c
urrent and cell shortening or intracellular Ca2+ transients were measu
red simultaneously in isolated whole-cell-clamped myocytes. The densit
y of the L-type Ca2+ current was smaller in myopathic than in normal m
yocytes (2.13+/-0.3 versus 3.21+/-0.4 pA/pF at 0 mV, P<.05). In both c
ontrol and myopathic myocytes, the L-type Ca2+ current gated the relea
se of Ca2+ and activation of contraction. In myopathic myocytes, activ
ation of contraction also activated a slowly inactivating inward curre
nt 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 dif
ferent 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 exc
hanger current in myopathic myocytes coincided with a significant prol
ongation of contraction and the intracellular Ca2+ transient and a del
ay in the onset of relaxation. These results suggest that the enhanced
activity of the Na+-Ca2+ exchanger may be related to compromised sequ
estration of Ca2+ in these animals.