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 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 (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 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.