Up-Regulation of Myocardial L-Type Ca2+ Channel in Chronic Alcoholic Subjects Without Cardiomyopathy

• Published in: Alcoholism, clinical and experimental research Vol. 31; no. 7; pp. 1099 - 1105
• Main Authors: Fatjó, Francesc, Sancho-Bru, Pau, Fernández-Solà, Joaquim, Sacanella, Emilio, Estruch, Ramón, Bataller, Ramón, Nicolás, Josep-María
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.07.2007; Lippincott Williams & Wilkins
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol Drinking - metabolism; Alcoholic Cardiomyopathy; Alcoholism; Alcoholism - epidemiology; Alcoholism - metabolism; Alcoholism and acute alcohol poisoning; Biological and medical sciences; Calcium Channels; Calcium Channels, L-Type - metabolism; Cardiology. Vascular system; Cardiomyopathy, Alcoholic - epidemiology; Cardiomyopathy, Alcoholic - metabolism; Cardiomyopathy, Alcoholic - pathology; Comorbidity; Ethanol; Ethanol - pharmacology; Female; Heart; Heart Transplantation; Humans; Male; Medical sciences; Middle Aged; Myocardial Contraction - drug effects; Myocarditis. Cardiomyopathies; Myocardium; Myocardium - metabolism; Myocardium - pathology; Organ Preservation; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Ryanodine - pharmacology; Ryanodine Receptor Calcium Release Channel - drug effects; Sarcoplasmic Reticulum; Tissue Donors; Toxicology; Up-Regulation - drug effects; Human; Calcium; Ethanol; Calcium Channels; Cardiomyopathy; Alcoholism; Cardiovascular disease; Ionic channel; Inorganic element; Myocardial disease; Alcoholic beverage; Chronic; Alcoholic Cardiomyopathy; Heart disease; Myocardium; Circulatory system; L-type calcium channel
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2007.00404.x

Background: Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. L‐type Ca2+ 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 Ca2+ channel receptors in organ donors with chronic alcoholism and controls. Methods: The protein expression of L‐type Ca2+ channels was determined with 3H‐(+)‐PN 200‐110‐binding experiments using a specific antibody against the α1‐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 Ca2+ channels expression in alcoholic patients compared with controls (Bmax 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 μm2, respectively; p<0.001 both) as was the perimeter (78.7 ± 7.7 vs 61.5 ± 7.2 and 56.5 ± 2.8 μm, 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 Ca2+ channel receptors, which decreases when cardiomyopathy is present.