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 arid 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). α-MHC was decreased relative to β-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.