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 (INa-Ca), because it was suppressed by rapid replacement of Na+ with Li+ and depletion of the intracellular Ca2+ pool by caffeine. INa-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.
Hatem
S N
SN
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
Sham
J S
JS
Morad
M
M
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D004594:Electrophysiology; D007425:Intracellular Membranes / Q000502:physiology; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction; D012016:Reference Values; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D012964:Sodium; D002118:Calcium