The effects of propofol on macroscopic and single channel sodium currents in rat ventricular myocytes.
1. The effects of the injectable anaesthetic agent propofol (di-isopropyl phenol) were examined on sodium currents and single sodium channels by use of patch-clamp techniques in ventricular myocytes isolated from rat hearts. 2. Propofol dose-dependently blocked the whole cell sodium currents evoked by a voltage step to -30 mV from a holding potential of -90 mV with an EC50 of 14.8+/-2.3 microM (mean+/-s.e.mean). 3. Propofol caused a substantial hyperpolarizing shift in the voltage-dependence of inactivation of sodium currents (168 microM (30 microg ml(-1)) propofol caused a -14 mV shift (P<0.01); 56 microM caused a -8 mV shift (P<0.05)). A smaller shift in the voltage-dependence of activation was produced (4 mV by 168 microM (not statistically significant)), but this was to more depolarized potentials. The maximal sodium conductance, as judged from the activation and inactivation curves, was reduced by 13% by 168 microM propofol (not statistically significant), but propofol did not affect the reversal potential of the current-voltage relationship. 4. The macroscopic rate of inactivation, as measured by the time constant of the exponential fall of current amplitude from the peak current, was also slowed by propofol, from a control time constant of 1.78+/-0.31 ms to 2.93+/-0.47 ms (mean+/-s.e.mean, n=8, P<0.05) by 168 microM propofol. Despite the increase in the time constant, the macroscopic inactivation remained well fitted by a single exponential. The macroscopic rate of activation was also slowed, but to a lesser degree (<10%, not statistically significant) by 168 microM propofol. 5. Propofol slowed the rate of recovery from inactivation of the sodium current, as measured by a two pulse protocol. Propofol (168 microM) increased the time constant of recovery, measured at -100 mV and room temperature, from a control value of 55+/-5.9 ms to 141+/-24.2 ms (mean+/-s.e.mean, n=8, P<0.01). Although the time constant was increased at all voltages measured, the intrinsic voltage-dependence of the rate of recovery was not changed. 6. Single channel recordings showed that the mean open time of single sodium channels was dramatically reduced by propofol (from 0.50+/-0.02 ms in control to 0.28+/-0.01 ms by 56 +/-M propofol and to 0.24+/-0.01 ms by 168 microM, both significantly different from control, P<0.01). Single channel conductance was not changed by either concentration of propofol.
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Department of Physiology, University of Adelaide, SA, Australia.
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
D018686:Anesthetics, Intravenous; D015222:Sodium Channels; D015742:Propofol