Anesthetic-sensitive ion channel modulation is associated with a molar water solubility cut-off

BMC Pharmacology & Toxicology
Robert J Brosnan, Trung L Pham

Abstract

NMDA receptor modulation by hydrocarbons is associated with a molar water solubility cut-off. Low-affinity phenolic modulation of GABAA receptors is also associated with a cut-off, but at much lower molar solubility values. We hypothesized that other anesthetic-sensitive ion channels exhibit distinct cut-off effects associated with hydrocarbon molar water solubility, and that cut-off values are comparatively similar between related receptors than phylogenetically distant ones. Glycine or GABAA receptors or TREK-1, TRESK, Nav1.2, or Nav1.4 channels were expressed separately in frog oocytes. Two electrode voltage clamp techniques were used to study current responses in the presence and absence of hydrocarbon series from eight functional groups with progressively increasing size at saturated aqueous concentrations. Null response (cut-off) was defined by current measurements that were statistically indistinguishable between baseline and hydrocarbon exposure. Ion channels exhibited cut-off effects associated with hydrocarbon molar water solubility in the following order of decreasing solubility: Nav1.2 ≈ Nav1.4 ≳ TRESK ≈ TREK-1 > GABAA > glycine. Previously measured solubility cut-off values for NMDA receptors were intermediate betw...Continue Reading

References

Dec 1, 1974·Journal of Pharmaceutical Sciences·G L AmidonS Leung
Jul 1, 1993·British Journal of Anaesthesia·N P Franks, W R Lieb
Mar 27, 1999·Neuroreport·R W Peoples, F F Weight
Dec 31, 2002·Anesthesia and Analgesia·Yi ZhangJames M Sonner
Jun 4, 2004·The EMBO Journal·C HeurteauxM Lazdunski
Apr 25, 2008·The Journal of Pharmacology and Experimental Therapeutics·Takafumi Horishita, R Adron Harris
Jul 28, 2010·Proceedings of the National Academy of Sciences of the United States of America·Grace BranniganMichael L Klein
Jan 8, 2011·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Stuart A Forman, Keith W Miller
Nov 1, 2011·The Journal of Pharmacology and Experimental Therapeutics·Cecilia M BorgheseR Adron Harris
Jul 1, 1985·Environmental Science & Technology·M CoatesD M Barron
Apr 6, 2012·Frontiers in Pharmacology·Karl F Herold, Hugh C Hemmings
Jan 5, 2014·Biochimica Et Biophysica Acta·Vasyl BondarenkoPei Tang
Nov 21, 2014·BMC Pharmacology & Toxicology·Robert J Brosnan, Trung L Pham
Jun 7, 2017·Veterinary Anaesthesia and Analgesia·Robert J BrosnanTrung L Pham

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Citations

Jun 20, 2020·Journal of Veterinary Pharmacology and Therapeutics·Robert J BrosnanScott D Stanley

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