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 single 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 potential. When cells were held at -90 mV, the EC50 was 2.8 micrograms/mL. When cells were held more hyperpolarized (at -140 mV), the EC50 increased to 44.0 micrograms/mL. 3. Although the degree of block produced by the same concentration of propofol was different at different holding potentials, the time course of onset and recovery from block was the same. 4. The current/voltage relationship for the sodium current showed a pronounced block of peak current by propofol (40-50% block of the maximum current by 30 micrograms/mL propofol), with a minimal shift in the voltage dependence of activation and no shift in reversal potential. 5. The voltage dependence of the steady state inactivation curve was shifted to more hyperpolarized potentials by propofol (shift of 18 and 8 mV by 30 and 10 micrograms/mL propofol, respectively). 6. Single channel records showed that propofol caused a shortening of the mean channel open time (from a mean of 0.59 to 0.38 ms by 10 micrograms/mL propofol), but no change in the channel amplitude. 7. It is concluded that propofol produces a block of sodium currents in cardiac myocytes at concentrations that are comparable to those that may be attained during anaesthesia.
Saint
D A
DA
Department of Physiology, University of Adelaide, South Australia, Australia. dsaint@physiol.adelaide.edu.au
Tang
Y
Y
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D026941:Sodium Channel Blockers
D018686:Anesthetics, Intravenous; D026941:Sodium Channel Blockers; D015742:Propofol