ryanodine and Alcoholism

Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. L-type Ca(2+) channels, involved in excitation-contraction coupling, are disturbed in animal models of persistent ethanol consumption. This study was designed to evaluate the density and function of myocardial L-type Ca(2+) channel receptors in organ donors with chronic alcoholism and controls.. The protein expression of L-type Ca(2+) channels was determined with (3)H-(+)-PN 200-110-binding experiments using a specific antibody against the alpha(1)-subunit in homogenate samples of left-ventricle apex from organ donors: healthy controls (n=11), chronic alcoholic without cardiomyopathy (n=12), and alcoholics with cardiomyopathy (n=11). Morphometric measurements of cardiomyocytes were performed.. Binding experiments proved an up-regulation of L-type Ca(2+) channels expression in alcoholic patients compared with controls (B(max) 2.61 +/- 1.10 vs 1.33 +/- 0.49 fmol/mg, respectively; p<0.001). This up-regulation was present in the group of alcoholic subjects without cardiomyopathy, and was not seen in those with cardiomyopathy (3.39 +/- 2.20 vs 1.77 +/- 0.53 fmol/mg, respectively; p=0.02). The cross-sectional area and perimeter of the cells were greater in alcoholic patients with cardiomyopathy compared with controls and alcoholic patients without cardiomyopathy (500 +/- 87 vs 307 +/- 74 and 255 +/- 25 microm(2), respectively; p<0.001 both) as was the perimeter (78.7 +/- 7.7 vs 61.5 +/- 7.2 and 56.5 +/- 2.8 microm, respectively; p<0.001 both). Binding results did not change after adjusting receptor measurements for cross-sectional area and cell perimeter.. Chronic alcoholism causes an up-regulation of myocardial L-type Ca(2+) channel receptors, which decreases when cardiomyopathy is present.

Topics: Alcohol Drinking; Alcoholism; Calcium Channels, L-Type; Cardiomyopathy, Alcoholic; Comorbidity; Ethanol; Female; Heart Transplantation; Humans; Male; Middle Aged; Myocardial Contraction; Myocardium; Organ Preservation; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Tissue Donors; Up-Regulation