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1.
Am J Physiol Cell Physiol ; 293(4): C1319-26, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17699638

ABSTRACT

Volatile anesthetics have been shown to activate various two-pore (2P) domain K(+) (K(2P)) channels such as TASK-1 and TREK-1 (TWIK-related acid-sensitive K(+) channel), and mice deficient in these channels are resistant to halothane-induced anesthesia. Here, we investigated whether K(2P) channels were also potentially important targets of intravenous anesthetics. Whole cell patch-clamp techniques were used to determine the effects of the commonly used intravenous anesthetics etomidate and propofol on the acid-sensitive K(+) current in rat ventricular myocytes (which strongly express TASK-1) and selected human K(2P) channels expressed in Xenopus laevis oocytes. In myocytes, etomidate decreased both inward rectifier K(+) (K(ir)) current (I(K1)) and acid-sensitive outward K(+) current at positive potentials, suggesting that this drug may inhibit TASK channels. Indeed, in addition to inhibiting guinea pig Kir2.1 expressed in oocytes, etomidate inhibited human TASK-1 (and TASK-3) in a concentration-dependent fashion. Propofol had no effect on human TASK-1 (or TASK-3) expressed in oocytes. Moreover, we showed that, similar to the known effect of halothane, sevoflurane and the purified R-(-)- and S-(+)-enantiomers of isoflurane, without stereoselectivity, activated human TASK-1. We conclude that intravenous and volatile anesthetics have dissimilar effects on K(2P) channels. Human TASK-1 (and TASK-3) are insensitive to propofol but are inhibited by supraclinical concentrations of etomidate. In contrast, stimulatory effects of sevoflurane and enantiomeric isoflurane on human TASK-1 can be observed at clinically relevant concentrations.


Subject(s)
Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Nerve Tissue Proteins/physiology , Potassium Channels, Tandem Pore Domain/physiology , Animals , Arachidonic Acids/pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Etomidate/pharmacology , Halothane/pharmacology , Humans , Hydrogen-Ion Concentration , Isoflurane/pharmacology , Membrane Potentials/drug effects , Methyl Ethers/pharmacology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/physiology , Nerve Tissue Proteins/genetics , Oocytes/drug effects , Oocytes/metabolism , Oocytes/physiology , Patch-Clamp Techniques , Potassium/metabolism , Potassium Channel Blockers/pharmacology , Potassium Channels, Tandem Pore Domain/genetics , Propofol/pharmacology , RNA, Complementary/genetics , Rats , Sevoflurane , Xenopus laevis
2.
J Phys Chem A ; 110(9): 3028-35, 2006 Mar 09.
Article in English | MEDLINE | ID: mdl-16509624

ABSTRACT

Energy transfer effects on dicarbon (C2) d3Pi(g) <-- a3Pi(u) laser-induced fluorescence (LIF) spectra in fuel-rich acetylene atmospheric-pressure flames have been studied using a combination of two different two-dimensional techniques. Measurements using a picosecond laser system in conjunction with a streak camera allowed determination of typical fluorescence lifetimes of levels in the d state and of population changes introduced by rotational energy transfer (RET) and by state-dependent quenching. Excitation-emission spectroscopy yielded two-dimensional maps containing all excitation and all emission spectra in the spectral ranges between 19 340 and 20 150 cm(-1) (excitation) and from 546 to 573 nm (emission) and allowed unambiguous assignment of all transitions in this spectral region. Our measurements show a comparatively long quenching lifetime (around 2 ns) and dominant effects of energy transfer on shape and intensity of the acquired spectra (90% of the fluorescence stems from levels populated by ET). A pronounced dependence of the total RET on the quantum number of the initially excited state is observed. Vibrational energy transfer (VET) is significantly weaker (only 5% contribution for excitation in the v' = 1 level). Implications for quantitative concentration measurements are discussed, and exemplary spatially resolved profiles in a well-characterized low-pressure propene flame are presented.

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