TOK1 Is a Volatile Anesthetic Stimulated K+Channel

Gray, Andrew T.; Winegar, Bruce D.; Leonoudakis, Dmitri; Forsayeth, John; Yost, Spencer

doi:10.1097/00000542-199804000-00029

Cited by 38 publications

(20 citation statements)

References 36 publications

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“…They can be affected by changes in internal and external pH, membrane stretch, temperature, arachidonic acid, as well as by a variety of internal second messenger systems. Of particular relevance to the present discussion is the fact that some members have been shown to be activated by volatile general anesthetics (Gray et al, 1998;Franks and Lieb, 1999;Patel et al, 1999;Patel and Honore, 2001a). This has been shown for both TASK and TREK members of the superfamily, although most work in this area has focused on the TASK channels, TASK-1 and TASK-3.…”

Section: Discussionmentioning

confidence: 88%

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Gruß

Bushell²,

Bright³

et al. 2004

Mol Pharmacol

286

192

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Nitrous oxide, xenon, and cyclopropane are anesthetic gases that have a distinct pharmacological profile. Whereas the molecular basis for their anesthetic actions remains unclear, they behave very differently to most other general anesthetics in that they have little or no effect on GABA A receptors, yet strongly inhibit the N-methyl-D-aspartate subtype of glutamate receptors. Here we show that certain members of the two-poredomain

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Section: Discussionmentioning

confidence: 88%

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Gruß

Bushell²,

Bright³

et al. 2004

Mol Pharmacol

286

192

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“…GAs generally suppress cell excitability in the CNS and this may occur through a concerted action on many targets, including sensitization/activation of K ϩ channels (Franks and Lieb, 1988;Gray et al, 1998;Patel et al, 1999) and GABA receptors (Nakahiro et al, 1991;Wakamori et al, 1991;Jones et al, 1992) and inhibition of N-methyl-D-aspartate receptors (Yamakura and Harris, 2000;Hollmann et al, 2001). Therefore, it may seem counterintuitive that GAs can excite peripheral sensory neurons.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to hypnosis or unconsciousness, most of these drugs also cause a varying degree of amnesia, muscle relaxation, and blunting of sympathetic responses (Miller et al, 2002). Although the precise molecular mechanisms are unresolved, several studies suggest that GAs can inhibit CNS activity by sensitizing or activating GABA A receptors (Nakahiro et al, 1991;Wakamori et al, 1991;Jones et al, 1992) and background K ϩ channels (Franks and Lieb, 1988;Gray et al, 1998;Patel et al, 1999) or by inhibiting glutamate receptors (Yamakura and Harris, 2000;Hollmann et al, 2001) and presynaptic transmitter release (van Swinderen et al, 1999).…”

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confidence: 99%

General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1

Cornett

Matta²,

Ahern³

2008

Mol Pharmacol

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General anesthetics (GAs) are central nervous system depressants that render patients unresponsive to external stimuli. In contrast, many of these agents are also known to stimulate peripheral sensory nerves, raising the possibility that they may exacerbate tissue inflammation. We have found that pungent GAs excite sensory neurons by directly activating the transient receptor potential (TRP) A1 ion channel. Here, we show that GAs also sensitize the capsaicin receptor TRPV1, a key ion channel expressed in nociceptive neurons. Clinically relevant concentrations of isoflurane, sevoflurane, enflurane, and desflurane sensitize TRPV1 to capsaicin and protons and reduce the threshold for heat activation. Furthermore, isoflurane directly activates TRPV1 after stimulation of protein kinase C. Likewise, isoflurane excites TRPV1 and sensory neurons during concomitant application of bradykinin, a key inflammatory mediator formed during tissue injury. Thus, GAs can enhance the activation of TRPV1 that occurs during surgically induced tissue damage. These results support the hypothesis that some GAs, through direct actions at TRP channels, increase postsurgical pain and inflammation.

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“…However, wild-type ScTok1p channels and a variety of other mutant variations have been expressed and studied in the Xenopus oocyte membranes without reports of major functional differences from the same channels in Saccharomyces membranes. Indeed, the oocyte system seems to have become the generally preferred site for characterizing yeast ScTok1p [14,20,25,28,32]. A simpler interpretation of the initial report is that the mutant channels failed to be expressed at functionally detectable levels for that experiment, absent a direct confirmation of the protein's presence in the oocyte membrane.…”

Section: Discussionmentioning

confidence: 99%

Functional consequences of leucine and tyrosine mutations in the dual pore motifs of the yeast K+ channel, Tok1p

Roller

Natura

Bihler

et al. 2008

Pflugers Arch - Eur J Physiol

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Tandem pore-loop potassium channels differ from the majority of K(+) channels in that a single polypeptide chain carries two K(+)-specific segments (P) each sandwiched between two transmembrane helices (M) to form an MP(1)M-MP(2)M series. Two of these peptide molecules assemble to form one functional potassium channel, which is expected to have biaxial symmetry (commonly described as asymmetric) due to independent mutation in the two MPM units. The resulting intrinsic asymmetry is exaggerated in fungal 2P channels, especially in Tok1p of Saccharomyces, by the N-terminal presence of four more transmembrane helices. Functional implications of such structural asymmetry have been investigated via mutagenesis of residues (L290 in P(1) and Y424 in P(2)) that are believed to provide the outermost ring of carbonyl oxygen atoms for coordination with potassium ions. Both complementary mutations (L290Y and Y424L) yield functional potassium channels having quasi-normal conductance when expressed in Saccharomyces itself, but the P(1) mutation (only) accelerates channel opening about threefold in response to depolarizing voltage shifts. The more pronounced effect at P(1) than at P(2) appears paradoxical in relation to evolution, because a comparison of fungal Tok1p sequences (from 28 ascomycetes) shows the filter sequence of P(2) (overwhelmingly TIGYGD) to be much stabler than that of P(1) (mostly TIGLGD). Profound functional asymmetry is revealed by the fact that combining mutations (L290Y + Y424L)-which inverts the order of residues from the wild-type channel-reduces the expressed channel conductance by a large factor (20-fold, cf.

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TOK1 Is a Volatile Anesthetic Stimulated K+Channel

Abstract: TOK1 is a potassium channel that is stimulated by volatile anesthetic agents. The concentrations over which potentiation occurred (EC50 values) were higher than those commonly used in clinical practice (approximately twice MAC).

Cited by 38 publications

References 36 publications

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1

Functional consequences of leucine and tyrosine mutations in the dual pore motifs of the yeast K+ channel, Tok1p

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TOK1 Is a Volatile Anesthetic Stimulated K+Channel

Abstract: TOK1 is a potassium channel that is stimulated by volatile anesthetic agents. The concentrations over which potentiation occurred (EC50 values) were higher than those commonly used in clinical practice (approximately twice MAC).

Cited by 38 publications

References 36 publications

Two-Pore-Domain K+ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Two-Pore-Domain K+ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

General Anesthetics Sensitize the Capsaicin Receptor Transient Receptor Potential V1

Functional consequences of leucine and tyrosine mutations in the dual pore motifs of the yeast K+ channel, Tok1p

Contact Info

Product

Resources

About

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane

Two-Pore-Domain K⁺ Channels Are a Novel Target for the Anesthetic Gases Xenon, Nitrous Oxide, and Cyclopropane