Reversible inhibition of intercellular communication among cardiac myocytes by halogenated hydrocarbons

Abstract

We examined the effect of 11 aliphatic halogenated hydrocarbons on the transfer of microinjected dye among cardiac myocytes from neonatal rats. Myocytes were suffused with increasing concentrations of halocarbon added as a 0.2% solution of dimethyl sulfoxide to M199 containing 1.8 m m Ca and 5% serum. Single cells were microinjected with the fluorescent probe Lucifer yellow (5% in 0.1 m m LiCl) and dye coupling to adjacent cells was monitored. All of the halocarbons tested exhibited a concentration-dependent inhibitory effect on intercellular communication that was reversible following washout of the compounds. Intercellular communication was blocked within 1 min of exposure to an effective concentration, and recovery of communication occured even after 2 hr of exposure. Pretreatment of cells with SKF 525-A (25 μM) did not prevent the inhibition of intercellular communication by carbon tetrachloride suggesting an absence of P-450 involvement. EC50s were calculated for each chemical using probit analysis. A log-log comparison of the EC50s and the physicochemical properties of the chemicals demonstrated a high correlation ( R 2 = 0.933) between the EC50s and the octanol/water partition coefficients of the halocarbons. This suggests that incorporation of halocarbons in the membrane may block intercellular communication though modification of the immediate environment of the gap junctions. The results are in agreement with the hypothesis that inhibition of gap junctional communication is a factor in the arrhythmogenic effects of acute halocarbon exposure.