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Effects of propofol on a Ca2+-activated CI- current in rabbit ventricular myocytes
1Department of Dental Anesthesiology, Faculty of Dentistry, Tokyo Medical and Dental University, Japan.
Abstract:
Propofol is a widely used intravenous anesthetic, which is known to affect cardiac functions. Cardiac effects may be caused by direct actions on ion channels of the heart. While effects of propofol on several ion channels have been studied at the whole cell and single-channel levels, its effects, if any, on anion currents have yet to be examined. Effects of propofol on Ca2+-activated Cl- current (I(Cl(Ca))) were investigated in single myocytes isolated from rabbit ventricles by the whole-cell patch clamp technique at 36 degrees C. I(Cl(Ca)) was activated by perfusing internal solutions with 0.1 microM free Ca2+ in the absence and presence of 10 mM internal Na+, eliciting I(Ca)-dependent and -independent component, respectively. By the application of propofol (0.1-300 microM), I(Ca)-independent I(Cl(Ca)) was strongly inhibited in a dose-dependent manner with an IC50 of about 5 microM. The blocking effects of propofol were voltage independent. On the other hand, the I(Ca)-dependent component of I(Cl(Ca)) was little affected by propofol at concentrations of up to 50 microM. The outward Na+/Ca2+ exchanger current was also blocked by application of 5 microM propofol. We conclude that propofol inhibits cardiac I(Cl(Ca)) in rabbit ventricular myocytes, mainly the I(Ca)-independent component, at therapeutic concentrations. The inhibition may be due to block of a reverse mode of Na+/Ca2+ exchange current.
Insights
Propofol, a common anesthetic, inhibits cardiac anion currents, specifically the calcium-activated chloride current (I(Cl(Ca))) in rabbit heart cells. This effect occurs at therapeutic concentrations and may involve blocking the sodium-calcium exchanger.
Area of Science:
- Cardiology
- Anesthesiology
- Molecular Pharmacology
Background:
- Propofol is a widely used intravenous anesthetic with known cardiac effects.
- Cardiac effects of propofol may stem from its actions on cardiac ion channels.
- The impact of propofol on cardiac anion currents remains largely unexamined.
Purpose of the Study:
- To investigate the effects of propofol on calcium-activated chloride currents (I(Cl(Ca))) in rabbit ventricular myocytes.
- To determine if propofol affects the calcium-dependent and independent components of I(Cl(Ca)).
- To explore the potential mechanism of propofol's action on cardiac ion channels.
Main Methods:
- Whole-cell patch clamp technique applied to single rabbit ventricular myocytes at 36°C.
- Activation of I(Cl(Ca)) using internal solutions with 0.1 μM free Ca2+.
- Application of varying concentrations of propofol (0.1–300 μM) to assess dose-dependent effects.
Main Results:
- Propofol significantly inhibited the I(Ca)-independent component of I(Cl(Ca)) in a dose-dependent manner (IC50 ≈ 5 μM).
- The I(Ca)-dependent component of I(Cl(Ca)) was minimally affected by propofol up to 50 μM.
- Propofol (5 μM) also blocked the outward Na+/Ca2+ exchanger current.
Conclusions:
- Propofol inhibits cardiac I(Cl(Ca)), particularly the I(Ca)-independent component, in rabbit ventricular myocytes at therapeutic concentrations.
- The observed inhibition may result from propofol blocking the reverse mode of the Na+/Ca2+ exchanger.
- These findings elucidate a novel mechanism for propofol's cardiac effects via anion current modulation.