The effect of high pressure on glycine- and kainate-sensitive receptor channels expressed in Xenopus oocytes.
The effect of high pressure on the response to glycine or kainate of voltage-clamped Xenopus oocytes micro-injected with messenger-RNA derived from either rat spinal cord or whole brain, respectively, has been investigated. Current responses were measured at 1 bar (= 10(5) Pa), 50 bar, 100 bar and 150 bar, with PO2 fixed at 1 bar and the balance helium. Glycine elicited a depolarizing current response which was antagonized by nanomolar concentrations of strychnine. The responses reversibly desensitized, with a decay constant of 0.01 s-1, when glycine concentrations greater than 250 microM were used. The decay constant was insensitive to both glycine concentration and pressure. Resensitization was complete within 4 min. Kainate elicited a depolarizing current which was non-desensitizing. The response was slightly sensitive to glutamate diethyl ester (50 microM), which increased the EC50 by 25%. The action of glycine was highly pressure sensitive. The dose-response curves established at 50 bar, 100 bar and 150 bar were shifted progressively to the right, with no effect on the maximal current. The EC50 increased from 216 microM to 296 microM at 50 bar, to 345 microM at 100 bar, and to 425 microM at 150 bar. The action of kainate was unaffected by pressure. No shift in the dose-response curves was established, nor was there any effect on the maximum current. The EC50 was 113 microM at 1 bar, and 111 microM at both 50 bar and 100 bar.(ABSTRACT TRUNCATED AT 250 WORDS)
Shelton
C J
CJ
Welsh School of Pharmacy, University of Wales College of Cardiff, U.K.
Doyle
M G
MG
Price
D J
DJ
Daniels
S
S
Smith
E B
EB
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000494:pharmacology*; D007473:Ion Channels / Q000096:biosynthesis / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011312:Pressure; D012333:RNA, Messenger / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine / Q000096:biosynthesis / Q000502:physiology; D018092:Kainic Acid Receptors / Q000096:biosynthesis / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*; D013331:Strychnine / Q000494:pharmacology; D014982:Xenopus laevis
D005998:Glycine; D007473:Ion Channels; D007608:Kainic Acid; D012333:RNA, Messenger; D018009:Receptors, Glycine; D018092:Kainic Acid Receptors; D013331:Strychnine