Up-regulation of myocardial L-type Ca2+ channel in chronic alcoholic subjects without cardiomyopathy.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Chronic alcoholism causes an up-regulation of myocardial L-type Ca(2+) channel receptors, which decreases when cardiomyopathy is present.
Fatjó
Francesc
F
Department of Internal Medicine, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Sancho-Bru
Pau
P
Fernández-Solà
Joaquim
J
Sacanella
Emilio
E
Estruch
Ramón
R
Bataller
Ramón
R
Nicolás
Josep-María
JM
D000428:Alcohol Drinking / Q000378:metabolism; D000437:Alcoholism / Q000453:epidemiology / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002310:Cardiomyopathy, Alcoholic / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D015897:Comorbidity; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009926:Organ Preservation; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D012519:Sarcoplasmic Reticulum; D014019:Tissue Donors; D015854:Up-Regulation / Q000187:drug effects
D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D000431:Ethanol