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 Ca(2+) handling, but no measurements of cytosolic Ca(2+) ([Ca(2+)](c)) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced changes in contractility are due to altered Ca(2+) handling by measuring [Ca(2+)](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 [Ca(2+)](c) (808 +/- 45 vs. 813 +/- 45 nM), diastolic [Ca(2+)](c) (195 +/- 11 vs. 193 +/- 10 nM), and rates of [Ca(2+)](c) rise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca(2+) handling proteins, sarcoplasmic reticulum Ca(2+)-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 Ca(2+) 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 Ca(2+) handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.