Up‐Regulation of Myocardial L‐Type Ca 2+ 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...
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Published in | Alcoholism, clinical and experimental research Vol. 31; no. 7; pp. 1099 - 1105 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.07.2007
|
Online Access | Get full text |
ISSN | 0145-6008 1530-0277 |
DOI | 10.1111/j.1530-0277.2007.00404.x |
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Summary: | 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
α
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
μ
m
2
, respectively;
p
<0.001 both) as was the perimeter (78.7 ± 7.7 vs 61.5 ± 7.2 and 56.5 ± 2.8
μ
m, 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. |
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ISSN: | 0145-6008 1530-0277 |
DOI: | 10.1111/j.1530-0277.2007.00404.x |