Comparison of calcium-current in isolated atrial myocytes from failing and nonfailing human hearts
Abstract To identify possible alterations of the L-type calcium currents (I Ca,L ) in cardiomyopathy, I Ca,L were recorded in atrial myocytes dissociated from the nonfailing heart (NF) of patients undergoing corrective open-heart surgery and explanted failing heart (FH) of patients with dilated cardiomyopathy undergoing heart transplantation. The patch-clamp technique was applied in the single-electrode whole-cell mode. The electrophysiological properties of I Ca,L , including cell capacitance and current density, were similar in atrial myocytes from both groups of patients. Further to identify possible alterations of the myocardial beta-adrenergic pathway in cardiomyopathy, we examined the effects of isoproterenol, forskolin, 8-Br-cAMP and IBMX on I Ca,L in both groups of atrial myocytes. Perfusion of isoproterenol (1 μM) significantly increased the peak I Ca,L by 515 ± 44% in 6 atrial myocytes from NF but increased only by 135 ± 25% in 27 atrial myocytes from FH. However, forskolin (1 μM) or 8-Br-cAMP (0.1 mM) increased the peak I Ca,L to a similar extent in atrial myocytes from NF and FH. IBMX (20 μM) also induced a comparable increase in the peak I Ca,L by 213 ± 31% (n=5) and 207 ± 59% (n=4) in atrial myocytes from NF and FH, respectively. The above findings suggest that in atrial myocytes obtained from FH the beta-adrenoceptor numbers might be decreased but no impairment of the signal transduction cascade occurred beyond the GTP binding proteins level.
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