METABOLIC INHIBITION OF CARDIOMYOCYTES CAUSES AN INCREASE IN SARCOLEMMAL FLUIDITY WHICH MAY BE DUE TO LOSS OF CELLULAR CHOLESTEROL

We examined whether metabolic inhibition (5 mM NaCN + 10 mM 2-deoxyglu cose) affects sarcolemmal fluidity in cultured neonatal cardiomyocytes . As a measure of sarcolemmal fluidity we determined the fluorescence steady-state anisotropy (r(ss), which is reciprocally related to membr ane fluidity) of cardiomyocytes labeled with rimethylammoniumphenyl)-6 -phenyl-1,3,5-hexatriene, p-toluenesulfonate. During metabolic inhibit ion, membrane fluidity increased progressively: after 30 min r(ss) had fallen by 6.7 +/- 1.2% (mean +/- SE; n = 9; P < 0.05) compared to bas eline values, and after 90 min by 14.5 + 3.5% (P < 0.05; n = 5). Beyon d 90 min r(ss) did not decrease any further. During control incubation s (without metabolic inhibition), no significant changes in r(ss) were observed. During metabolic inhibition cellular free cholesterol conte nt declined: after 30 min free cholesterol content had decreased by 12 .2 +/- 3.1% (P < 0.02; n = 4), compared to baseline values, and after 90 min by 31.1 + 8.3% (P < 0.02; n = 4). We conclude that metabolic in hibition induces an increase in sarcolemmal fluidity, which may be cau sed by a decrease in sarcolemmal free cholesterol content. (C) 1995 Ac ademic Press, Inc.