PROPOFOL BLOCK OF CARDIAC SODIUM CURRENTS IN RAT ISOLATED MYOCARDIAL-CELLS IS INCREASED AT DEPOLARIZED RESTING POTENTIALS

1. The effect of propofol on cardiac whole-cell sodium currents and si ngle sodium channels in rat isolated ventricular myocytes was examined using patch-clamp techniques. 2. Propofol caused a block of the whole -cell sodium current, the potency of block depending on the holding po tential. When cells were held at -90 mV, the EC50 was 2.8 mu g/mL. Whe n cells were held more hyperpolarized (at -140mV), the EC50 increased to 44.0 mu g/mL. 3. Although the degree of block produced by the same concentration of propofol was different at different holding potential s, the time course of onset and recovery from block was the same. 4. T he current/voltage relationship for the sodium current showed a pronou nced block of peak current by propofol (40-50% block of the maximum cu rrent by 30 mu g/mL propofol), with a minimal shift in the voltage dep endence of activation and no shift in reversal potential. 5. The volta ge dependence of the steady state inactivation curve was shifted to mo re hyperpolarized potentials by propofol (shift of 18 and 8 mV by 30 a nd 10 mu g/mL propofol, respectively). 6. Single channel records showe d that propofol caused a shortening of the mean channel open time (fro m a mean of 0.59 to 0.38 ms by 10 mu g/mL, propofol), but no change in the channel amplitude. 7. It is concluded that propofol produces a bl ock of sodium currents in cardiac myocytes at concentrations that are comparable to those that may be attained during anaesthesia.