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Updated: Sep 10, 2026
Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Anesthetic sensitivities to propofol and halothane in mice lacking the R-type (Cav2.3) Ca2+ channel
Tetsuhiro Takei1, Hironao Saegusa, Shuqin Zong
1Department of Anesthesiology, Graduate School of Medicine, Tokyo Medical and Dental University, Japan.
Unlabelled:
Because inhibition of voltage-dependent Ca(2+) channels can be a mechanism underlying general anesthesia, we examined sensitivities to propofol and halothane in mice lacking the R-type (Ca(v)2.3) channel widely expressed in neurons. Sleep time after propofol injection (26 mg/kg IV) and halothane MAC(RR) and MAC (50% effective concentrations for the loss of the righting reflex and for the tail pinch/withdrawal response, respectively) were determined. Significantly shorter propofol-induced sleep time (291.6 +/- 16.8 s versus 344.4 +/- 12.1 s) and larger halothane MAC(RR) (1.11% +/- 0.04% versus 0.98% +/- 0.03%) were observed in Ca(v)2.3 channel knockouts (Ca(v)2.3(-/-)) than in wild-type (Ca(v)2.3(+/+)) litter mates. To investigate the basis of the decreased anesthetic sensitivities in vivo, field excitatory postsynaptic potentials and population spikes (PSs) were recorded from Schaffer collateral CA1 synapses in hippocampal slices. Propofol (10-30 micro M) inhibited PSs by potentiating gamma-aminobutyric acid-ergic inhibition, and this potentiation was markedly smaller at 30 micro M in Ca(v)2.3(-/-) mice, possibly accounting for the decreased propofol sensitivity in vivo. Halothane (1.4%-2.2%) inhibited field excitatory postsynaptic potentials similarly in both genotypes, whereas 1%-2% halothane depressed PSs more in Ca(v)2.3(-/-) mice, suggesting the postsynaptic role of the R-type channel in the propagation of excitation and other mechanisms underlying the increased halothane MAC(RR) in Ca(v)2.3(-/-) mice.
Implications:
Because inhibition of neuronal Ca(2+) currents can be a mechanism underlying general anesthesia, we examined anesthetic sensitivities in mice lacking the R-type (Ca(v)2.3) Ca(2+) channels both in vivo and in hippocampal slices. Decreased sensitivities in mutant mice imply a possibility that agents blocking this channel may increase the requirements of anesthetics/hypnotics.
Insights
Mice lacking the R-type (Ca(v)2.3) calcium channels showed reduced sensitivity to general anesthetics like propofol and halothane. This suggests that blocking these channels may increase anesthetic requirements.
Area of Science:
- Neuroscience
- Anesthesiology
- Ion Channel Physiology
Background:
- Voltage-dependent Ca(2+) channels play a role in general anesthesia.
- The R-type (Ca(v)2.3) channel is widely expressed in neurons and its function in anesthesia is not fully understood.
Purpose of the Study:
- To investigate the role of the R-type (Ca(v)2.3) calcium channel in anesthetic sensitivity.
- To determine the effects of propofol and halothane on mice lacking Ca(v)2.3 channels.
Main Methods:
- Anesthetic sensitivities (propofol sleep time, halothane MAC) were measured in Ca(v)2.3 knockout mice and wild-type littermates.
- Electrophysiological recordings (field excitatory postsynaptic potentials, population spikes) were performed in hippocampal slices.
Main Results:
- Ca(v)2.3 knockout mice exhibited significantly shorter propofol-induced sleep times and higher halothane MAC values.
- In hippocampal slices, propofol's potentiation of GABAergic inhibition was reduced in knockout mice.
- Halothane's depression of population spikes was more pronounced in knockout mice, suggesting a postsynaptic role for Ca(v)2.3 channels.
Conclusions:
- The R-type (Ca(v)2.3) calcium channel contributes to the anesthetic effects of propofol and halothane.
- Inhibition of neuronal Ca(2+) currents via Ca(v)2.3 channels may be a key mechanism in general anesthesia.
- Targeting Ca(v)2.3 channels could influence anesthetic requirements.
