Comparison of calcium-current in isolated atrial myocytes from failing and nonfailing human hearts.
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 microM) 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 microM) 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 microM) 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.
Cheng
T H
TH
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Lee
F Y
FY
Wei
J
J
Lin
C I
CI
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology* / Q000601:surgery; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005576:Colforsin / Q000494:pharmacology; D001026:Coronary Artery Bypass; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D006325:Heart Atria; D016027:Heart Transplantation; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D015398:Signal Transduction
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D005576:Colforsin; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine