Chronic alcohol-induced changes in cardiac contractility are not due to changes in the cytosolic Ca2+ transient.
Long-standing heavy alcohol consumption acts as a chronic stress on the heart. It is thought that alcohol-induced changes of contractility are due to altered Ca2+ handling, but no measurements of cytosolic Ca2+ ([Ca2+]c) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced changes in contractility are due to altered Ca2+ handling by measuring [Ca2+]c (indo 1) in hearts from rats drinking 36% ethanol for 7 mo and age-matched controls. Peak left ventricular pressure was depressed (-16%), whereas rates of contraction (12%) and relaxation (14-20%) were faster in alcohol-exposed hearts. Systolic [Ca2+]c (808 +/- 45 vs. 813 +/- 45 nM), diastolic [Ca2+]c (195 +/- 11 vs. 193 +/- 10 nM), and rates of [Ca2+]c rise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca2+-handling proteins, sarcoplasmic reticulum Ca2+-ATPase and phospholamban, were the same in myocytes isolated from alcohol-exposed and control hearts (SDS-polyacrylamide gel). These data suggest that chronic alcohol-induced contractile changes are not due to altered Ca2+ handling but may be due to changes at the level of the myofilament. As a first step in elucidating the mechanism(s) of alcohol-induced changes at the myofilament, we assessed myosin heavy chain (MHC) isoform content (SDS-polyacrylamide gel). alpha-MHC was decreased relative to beta-MHC (a/a + b = 0.55 +/- 0.03 vs. 0.66 +/- 0.02; P < 0.02) in alcohol-exposed hearts, which cannot account for the observed alcohol-induced contractile changes. In conclusion, changes of myocardial contractility due to chronic alcohol exposure do not result from altered Ca2+ handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.
Department of Medicine (Cardiology), San Francisco General Hospital, San Francisco, California 94110, USA.
V M
VM
Figueredo
K C
KC
Chang
A J
AJ
Baker
S A
SA
Camacho
D000428:Alcohol Drinking / Q000378:metabolism / Q000503:physiopathology*; D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002304:Cardiac Pacing, Artificial; D003600:Cytosol / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D000099211:Phospholamban