Modulation by Extracellular Ph of Gaba_A Receptors Expressed in Xenopus Oocytes Injected with Rat Brain Mrna

Abstract

Rat brain poly(A)' mRNA was injected into Xenopus oocytes. After 72-%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 tlunitrazepam. Acidic (6.4) extracellular pH (pH_e) augmented, whereas basic pH (8.4) decreased the current evoked by 100μM 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 /_maz in comparison to pH 7.4. At pH 8.4 there was a significant decrease of FC50 for GABA. However, there was also a very strong decrease of /_max. so that the overall effect at lOOuM 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.

Key Words:

• Rat brain
• mRNA
• Xenopus oocytes
• GABA
• GABAA receptors
• pH