Modulation of Noninactivating K+ Channels in Rat Cerebellar Granule Neurons by Halothane, Isoflurane, and Sevoflurane

Shin, WooJong; Winegar, Bruce D.

doi:10.1213/01.ane.0000055365.31940.0a

Cited by 18 publications

(14 citation statements)

References 26 publications

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“…The self-desensitizing effect could be a result of “halo-dumping” [41] in which the higher ratings on the untreated side of the mouth could have reflected scores in which panelists combined ratings for tingle and burning sensations. Alternatively, the KCNK two-pore potassium channels identified as being central to eliciting tingle [11] have also been implicated as having a role in anesthesia [11], [42].…”

Section: Discussionmentioning

confidence: 99%

Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle

Albin

Simons²

2010

PLoS ONE

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Previous studies investigated the neural and molecular underpinnings of the tingle sensation evoked by sanshool and other natural or synthetic alkylamides. Currently, we sought to characterize the psychophysical properties associated with administration of these compounds. Like other chemesthetic stimuli, the synthetic tingle analog isobutylalkylamide (IBA) evoked a sensation that was temporally dynamic. Repeated IBA application at short (30 sec) interstimulus intervals (ISI) resulted in a tingle sensation that increased across trials. Application at longer ISIs (∼30 min) resulted in a sensation of decreased intensity consistent with self-desensitization. Prior treatment with the TRPV1 or TRPA1 agonists, capsaicin and mustard oil did not cross-desensitize the tingle sensation evoked by IBA suggesting that neither TRPV1 nor TRPA1 participate in the transduction mechanism sub-serving tingle. When evaluated over 30-min time period, lingual IBA evoked a sensation that was described initially as tingling and pungent but after approximately 15 min, as a cooling sensation. Further, we found that the sensation evoked by lingual IBA was potentiated by simultaneous application of cold (0°C) and cool (21°C) thermal stimuli but was unaffected by warm (33°C) and hot (41°C) temperatures. Finally, to test the hypothesis that the tingling sensation is subserved by the activation of mechanosensitve fibers, we evaluated lingual tactile thresholds in the presence and absence of lingual IBA. The presence of IBA significantly raised lingual tactile thresholds, whereas capsaicin did not, identifying a role for mechanosensitive fibers in conveying the tingle sensation evoked by sanshool-like compounds. Collectively, these results show that lingual alkylamide evokes a complex sensation that is temporally dynamic and consistent with in vitro and in vivo experiments suggesting these compounds activate mechanosensitve neurons via blockade of KCNK two-pore potassium channels to induce the novel tingling sensation.

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Section: Discussionmentioning

confidence: 99%

Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle

Albin

Simons²

2010

PLoS ONE

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“…In rat somatic motoneurons and locus ceruleus neurons that both express TASK-1 mRNA, halothane (EC 50 0.23 mmol/L) and sevoflurane (EC 50 0.29 mmol/L) induced hyperpolarization and current activation (Sirois et al, 2000). Similar background K + current activating effects in rat cerebellar granule neurons were demonstrated for clinically relevant concentrations of halothane, isoflurane, and sevoflurane (Shin et al, 2003).…”

Section: Neuronal Two-pore Domain Potassium Channelsmentioning

confidence: 59%

“…The physiology and pharmacology of these fascinating neuronal background or twopore-domain K + channels soon became the subject of intense research efforts and several reviews have been published (e.g., Yost, 2000Yost, , 2003Lesage, 2003). In particular, members of the TREK and TASK subfamilies are expressed in specific neuronal cells (Patel et al, 1999;Sirois et al, 2000;Washburn et al, 2002) and are differentially activated by volatile anesthetics at clinically relevant concentrations (Patel et al, 1999;Sirois et al, 2000;Shin et al, 2003). For example, heterologously expressed TREK-1 was activated in a concentration-dependent manner (range 0.1-1.0 mmol/L) by halothane, isoflurane, chloroform, and diethyl ether, whereas TASK channels were sensitive to halothane and isoflurane, but insensitive to chloroform and diethyl ether (Patel et al, 1999).…”

Section: Neuronal Two-pore Domain Potassium Channelsmentioning

confidence: 99%

Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Himmel

2008

Critical Reviews in Toxicology

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An increased sensitivity of the heart to catecholamines or cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. Although cardiac sensitization to such "industrial" halocarbons can result in serious arrhythmia and death, research into its mechanistic basis has been limited, whereas the literature on volatile anesthetics (e.g., halothane, chloroform) is comparably extensive. A review of the literature on halocarbons and related volatile anesthetics was conducted. The available experimental evidence suggests that volatile anesthetics at physiologically relevant concentrations interact predominantly with the main repolarizing cardiac potassium channels hERG and I Ks , as well as with calcium and sodium channels at slightly higher concentrations. On the level of the heart, inhibition of these ion channels is prone to alter both action potential shape (triangulation) and electrical impulse conduction, which may facilitate arrhythmogenesis by volatile anesthetics per se and is potentiated by catecholamines. Action potential triangulation by regionally heterogeneous inhibition of calcium and potassium channels will facilitate catecholamine-induced afterdepolarizations, triggered activity, and enhanced automaticity. Inhibition of cardiac sodium channels will reduce conduction velocity and alter refractory period; this is potentiated by catecholamines and promotes reentry arrhythmias. Other cardiac and/or neuronal mechanisms might also contribute to arrhythmogenesis. The few scattered in vitro data available for halocarbons (e.g., FC-12, halon 1301, trichloroethylene) suggest inhibition of cardiac sodium (conduction), calcium and potassium channels (triangulation), extraneuronal catecholamine reuptake, and various neuronal ion channels. Therefore, it is hypothesized that halocarbons promote cardiac sensitization by similar mechanisms as volatile anesthetics. Experimental approaches for further investigation of these sensitization mechanisms by selected halocarbons are suggested.

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“…Effects of different inhaled anesthetics on ion channel (e.g., K ? ) [12,13] as well as in different receptors [14] have also been reported. In these biophysical studies, the concentrations of halothane, isoflurane, and sevoflurane were determined by gas chromatography [10].…”

Section: Anesthetic and Protein Interactionmentioning

confidence: 82%

Clinically Relevant Concentration Determination of Inhaled Anesthetics (Halothane, Isoflurane, Sevoflurane, and Desflurane) by 19F NMR

Mandal

Pettegrew

2008

Cell Biochem Biophys

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Biophysical studies of protein-anesthetic interactions using nuclear magnetic resonance (NMR) spectroscopy are often conducted by the addition of micro amounts of neat inhaled anesthetic which yields much higher than clinically relevant (0.2-0.5 mM) anesthetic concentrations. We report a 19F NMR technique to measure clinically relevant inhaled anesthetic concentrations from saturated aqueous solutions of these anesthetics (halothane, isoflurane, sevoflurane, and desflurane). We use a setup with a 3-mm NMR tube (containing trifluoroacetic acid as standard), coaxially inserted in a 5-mm NMR tube containing anesthetic solution under investigation. All experiments are conducted in a 5-mm NMR probe. We also have provided standard curves for four inhaled anesthetics using NMR technique. The standard curve for each of these anesthetics is helpful in determining the prerequisite amount of aqueous anesthetic solution required to prepare clinically relevant concentrations for protein-anesthetic interaction studies.

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Modulation of Noninactivating K+ Channels in Rat Cerebellar Granule Neurons by Halothane, Isoflurane, and Sevoflurane

Abstract: The volatile anesthetics halothane, isoflurane, and sevoflurane, reversibly enhanced a noninactivating outwardly rectifying K(+) current in rat cerebellar granule neurons. These findings support a model of anesthesia that includes a site of action at baseline K(+) channels.

Cited by 18 publications

References 26 publications

Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle

Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle

Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Clinically Relevant Concentration Determination of Inhaled Anesthetics (Halothane, Isoflurane, Sevoflurane, and Desflurane) by 19F NMR

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