Volatile anesthetic inhibition of neuronal Ca channel currents expressed in Xenopus oocytes

Kamatchi, Ganesan L.; Chan, Carrie K.; Snutch, Terry P.; Durieux, Marcel E.; Lynch, Carl

doi:10.1016/s0006-8993(99)01401-8

Cited by 46 publications

(33 citation statements)

References 53 publications

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“…The effect of VAs on [Ca 2 + ]i peak and plateau in neurons pretreated with both nicardipine and Ctx-GVIA, or the IBa in similarly treated voltage clamped GCs, showed marked inhibition of the remaining response, suggesting that P/Q-and Rtype VGCC are relatively sensitive to the VAs. After specifically blocking one or more of the various VGCC types, the VAs always had an effect on the remaining channels, consistent with our previous observation that the VA's inhibited the various types of VGCC to a similar extent when the specific associated α1 subunit was expressed in oocytes (α1Α =P/Q-type; α1B=N-type; α1C=L-type; α1E=R-type) (19).…”

Section: Discussionsupporting

confidence: 90%

“…Four distinct ion conducting α Ca channel subunits have been defined by molecular biologic techniques that correspond to these electrophysiological types: CaV1.2 (L-type, αC), CaV 2.1 (P and Q are splice variants, αA), CaV 2.2 (N-type, αB), and CaV 2.3 (R-type, αE) (18). We have previously demonstrated the ability of VA's to depress Ca 2+ currents through all four channels types when expressed in Xenopus oocytes (19). The present study was undertaken to determine to what extent VAs alter [Ca 2+ ]i transients in CG neurons mediated by these multiple types of VGCCs, and the resulting glutamate release evoked by the Ca 2+ entry.…”

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confidence: 99%

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Volatile Anesthetic Depression of Ca2+ Entry Into and Glutamate Release from Cultured Cerebellar Granule Neurons

Lynch¹,

Miao²,

Nagao³

et al. 2017

J Anesth Perioper Med

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Volatile Anesthetic Depression of Ca2+ Entry Into and Glutamate Release from Cultured Cerebellar Granule Neurons

Lynch¹,

Miao²,

Nagao³

et al. 2017

J Anesth Perioper Med

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“…These drugs decrease the amplitude of both peak and residual (similar to "end current" here) Ca 2ϩ currents, shift Ca 2ϩ current inactivation to hyperpolarizing potentials, and increase the inactivation rate of native VSCCs in hippocampal (Study, 1994) and dorsal root ganglion neurons (Kameyama et al, 1999) as well as VSSC-expressed in oocytes (Kamatchi et al, 1999). One difference between the VOCs and volatile anesthetics is the ability of the former to shift the activation potential to more hyperpolarized potentials.…”

Section: Discussionmentioning

confidence: 99%

“…Alcohol and volatile anesthetics have been demonstrated to disrupt function of VSCCs (Study, 1994;Kamatchi et al, 1999;Kameyama et al, 1999;McMahon et al, 2000), and this action has been suggested to contribute to effects of these compounds on the nervous system. The present studies were designed to test further the hypothesis that VOCs interact with VSCCs.…”

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confidence: 99%

Perturbation of Voltage-Sensitive Ca2+ Channel Function by Volatile Organic Solvents

Shafer¹,

Bushnell²,

Benignus³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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The mechanisms underlying the acute neurophysiological and behavioral effects of volatile organic compounds (VOCs) remain to be elucidated. However, the function of neuronal ion channels is perturbed by VOCs. The present study examined effects of toluene (TOL), trichloroethylene (TCE), and perchloroethylene (PERC) on whole-cell calcium current (I Ca ) in nerve growth factor-differentiated pheochromocytoma (PC12) cells. All three VOCs affected I Ca in a reversible, concentration-dependent manner. At ϩ10-mV test potentials, VOCs inhibited I Ca , whereas at test potentials of Ϫ20 and Ϫ10 mV, they potentiated it. The order of potency for inhibition (IC 50 ) was PERC (270 M) Ͼ TOL (720 M) Ͼ TCE (1525 M). VOCs also changed I Ca inactivation kinetics from a single-to double-exponential function. Voltage-ramp experiments suggested that VOCs shifted I Ca activation in a hyperpolarizing direction; this was confirmed by calculating the half-maximal voltage of activation (V 1/2, act ) in the absence and presence of VOCs using the Boltzman equation. V 1/2, act was shifted from approximately Ϫ2 mV in control to Ϫ11, Ϫ12, and Ϫ16 mV by TOL, TCE, and PERC, respectively. Similarly, VOCs shifted the half-maximal voltage of steady-state inactivation (V 1/2, inact ) from approximately Ϫ16 mV in control to Ϫ32, Ϫ35, and Ϫ20 mV in the presence of TOL, TCE, and PERC, respectively. Inhibition of I Ca by TOL was confirmed in primary cultures of cortical neurons, where 827 M TOL inhibited current by 61%. These data demonstrate that VOCs perturb voltage-sensitive Ca 2ϩ channel function in neurons, an effect that could contribute to the acute neurotoxicity of these compounds.Volatile organic compounds (VOCs), such as toluene (

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“…Taken together, this suggests that the halothane-induced decrease in mEPSC and mIPSC frequency may be the result of a reduction in presynaptic calcium channel activity or by an interference with the calciumdependent proteins that mediate vesicular-membrane fusion. It was indeed shown that various types of voltage-gated calcium channels were inhibited by volatile anesthetics such as halothane and isoflurane and intravenous anesthetics such as propofol (Asahina et al, 1998;Nikonorov et al, 1998;Hirota et al, 1999;Kamatchi et al, 1999Kamatchi et al, , 2001Kameyama et al, 1999;McDowell et al, 1999;Camara et al, 2001;Hü neke et al, 2001;Yamakage and Namiki, 2002).…”

Section: Discussionmentioning

confidence: 99%

Effects of Halothane and Propofol on Excitatory and Inhibitory Synaptic Transmission in Rat Cortical Neurons

Kitamura

Marszalec²,

Yeh³

et al. 2003

The Journal of Pharmacology and Experimental Therapeutics

100

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General anesthetics are thought to act on both excitatory and inhibitory neuronal pathways at both post-and presynaptic sites. However, the literature in these regards is somewhat controversial. The aim of the present study was to reassess the relative importance of the various anesthetic actions using a common preparation. Rat cortical neurons in primary culture were used to record spontaneous miniature postsynaptic currents by the whole-cell patch-clamp technique. Halothane at clinically relevant concentrations prolonged the decay phase of spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in the presence of tetrodotoxin and at higher concentrations decreased the frequency of mIPSCs. The mIPSC amplitudes underwent little change. Spontaneous action potential-dependent IPSCs recorded in the absence of tetrodotoxin were similarly affected by halothane. Halothane also decreased the frequency of spontaneous miniature non-N-methyl-D-aspartate (NMDA) excitatory postsynaptic currents (mEPSCs) as well as spontaneous action potential-dependent NMDA EPSCs and non-NMDA EPSCs without affecting their decay phase. The halothane effect on mIPSC and mEPSC frequency was dependent on the external calcium concentration. In contrast to halothane, the only effect of propofol was the prolongation of the decay phase of mIPSCs and IPSCs. The prolongation of mIPSCs and IPSCs by halothane and propofol coupled with the ineffectiveness on mEPSCs and EPSCs suggests a selective postsynaptic modulation of GABA A receptors. The additional calcium-dependent inhibition of mIPSC and mEPSC frequency by halothane (but not propofol) suggests a more general mechanism by this anesthetic on presynaptic transmitter release.

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Volatile anesthetic inhibition of neuronal Ca channel currents expressed in Xenopus oocytes

Cited by 46 publications

References 53 publications

Volatile Anesthetic Depression of Ca2+ Entry Into and Glutamate Release from Cultured Cerebellar Granule Neurons

Volatile Anesthetic Depression of Ca2+ Entry Into and Glutamate Release from Cultured Cerebellar Granule Neurons

Perturbation of Voltage-Sensitive Ca2+ Channel Function by Volatile Organic Solvents

Effects of Halothane and Propofol on Excitatory and Inhibitory Synaptic Transmission in Rat Cortical Neurons

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