Modulation by extracellular pH of GABAA receptors expressed in Xenopus oocytes injected with rat brain mRNA.
Rat brain poly(A)(+) mRNA was injected into Xenopus oocytes. After 72-96 hr, GABA(A) receptors expressed in this heterologous system were studied by perfusion of GABA and recording of GABA evoked chloride current under voltage-clamp conditions. The GABA activated currents were blocked by bicuculline and enhanced by flunitrazepam. Acidic (6.4) extracellular pH (pH(e) ) augmented, whereas basic pH (8.4) decreased the current evoked by 100 microM GABA in the respect of the current evoked at pH 7.4. Concentration-response curves for GABA evoked chloride currents were built at the three pHs. These data showed that acidic pH does not change the EC50 for GABA but it increases significantly I(max) in comparison to pH 7.4. At pH 8.4 there was a significant decrease of EC50 for GABA. However, there was also a very strong decrease of I(max), so that the overall effect at 100 microM GABA was a decrease of GABA activated chloride current in the respect of the one activated at neutral pH. These data may indicate that on average brain GABA(A) receptors are positively modulated by extracellular acidosis. The opposite may occur in extracellular alcalosis.
Robello
M
M
Unità INFM, Dipartimento di Fisica, Università di Genova, C.N.R., Genoa, Italy. robello@ge.infm.it
Balduzzi
R
R
Cupello
A
A
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005445:Flunitrazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009865:Oocytes / Q000502:physiology; D012333:RNA, Messenger / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D018756:GABA Antagonists; D018757:GABA Modulators; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D001640:Bicuculline