Ethanol acutely and reversibly suppresses excitation-contraction coupling in cardiac myocytes.
We used adult rat cardiac myocytes to examine the acute effects of 0.1-5.0% (vol/vol) ethanol (ETOH) on 1) the cytosolic [Ca2+] (Cai) transient measured as the change in indo 1 fluorescence at 410/490 nm and contraction elicited by electrical stimulation of single cells and 2) the sarcoplasmic reticulum (SR) Ca2+ content in cell suspensions. During stimulation at 1 Hz, clinically relevant ETOH correlations (0.1-0.15% [vol/vol]) caused a 10-15% decrease in the contraction amplitude, measured by myocyte edge tracking, without decreasing the Cai transient that initiates contraction. At higher ETOH concentrations (1-5% [vol/vol]), ETOH caused profound contractile depression and also reduced the magnitude of the Cai transient. These effects were reversed within minutes of ETOH washout. Addition of norepinephrine (10 microM) to the bathing solution or an increase in bathing [Ca2+] in the continued presence of ETOH could also reverse its effects. The relation of the amplitude of the Cai transient to the contraction amplitude measured across a range of bathing [Ca2+] was shifted by ETOH, such that for a given Cai transient a marked reduction in contraction amplitude occurred. In unstimulated myocyte suspensions, ETOH (1-5% [vol/vol]) caused a concentration-dependent depletion of SR Ca2+ content, manifested as a diminution in the Cai increase elicited by caffeine in the presence of extracellular EGTA and no added Ca2+. Thus, in rat cardiac myocytes a reduction in the myofilament Ca2+ response, possibly due to a decrease in myofilament Ca2+ sensitivity, is a mechanism for contractile depression due to clinically relevant ETOH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Danziger
R S
RS
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD.
Sakai
M
M
Capogrossi
M C
MC
Spurgeon
H A
HA
Hansford
R G
RG
Lakatta
E G
EG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D003600:Cytosol / Q000378:metabolism; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D051381:Rats
D000431:Ethanol; D002118:Calcium