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The general anesthetic propofol inhibits transmembrane calcium current in chick sensory neurons
R Olcese1, C Usai, E Maestrone
1Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas.
Abstract:
The action of propofol on voltage-gated calcium channels was investigated in cultured dorsal root ganglion neurons from chick embryos. The Ca2+ current was measured by using the patch-clamp technique in whole cell configuration. Low-voltage-activated (LVA) and high-voltage-activated (HVA) Ca2+ currents were selected by means of appropriate stimulation protocols. Propofol (0.3 mM) inhibited the LVA T-type current by 80% (P < 0.001). The same concentration of propofol reduced the HVA Ca2+ current with a high variability (10%-75%). The inactivation time constant of the HVA current was also shortened to 50% by propofol. omega-Conotoxin and nifedipine were used to discriminate between the HVA N- and L-type current components. Only the L-type component was strongly depressed (75%) by propofol (P < 0.001); different effects on the HVA current might, therefore, reflect different percentages of L- and N-type channels in neurons. We conclude that propofol inhibits the T-type and L-type components of the Ca2+ current. This inhibition may play a role in the cardiovascular side effects clinically observed.
Insights
Propofol significantly inhibits low-voltage-activated T-type and high-voltage-activated L-type calcium currents in neurons. This action may explain propofol
Area of Science:
- Neuroscience
- Pharmacology
- Ion Channel Physiology
Background:
- Propofol is a widely used anesthetic agent.
- Its precise mechanisms of action, particularly on neuronal ion channels, require further elucidation.
- Voltage-gated calcium channels play critical roles in neuronal excitability and neurotransmitter release.
Purpose of the Study:
- To investigate the effects of propofol on different types of voltage-gated calcium channels.
- To determine the specific components of calcium currents affected by propofol in dorsal root ganglion neurons.
Main Methods:
- Utilized the patch-clamp technique in whole-cell configuration on cultured chick embryo dorsal root ganglion neurons.
- Measured low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium currents.
- Employed specific stimulation protocols and pharmacological agents (omega-conotoxin, nifedipine) to differentiate calcium channel subtypes.
Main Results:
- Propofol (0.3 mM) strongly inhibited the LVA T-type calcium current by 80%.
- Propofol also inhibited the HVA calcium current, with effects ranging from 10% to 75%.
- Propofol predominantly inhibited the L-type calcium current component (75%) within the HVA currents.
Conclusions:
- Propofol inhibits both T-type and L-type calcium currents.
- This inhibition of specific calcium channel subtypes may contribute to the observed cardiovascular side effects of propofol.