Properties of GABA(A) receptors in cultured rat oligodendrocyte progenitor cells.
We have studied the properties of GABA responses in oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells derived from primary cultures of the neonatal rat brain. In whole cell voltage clamp recordings, rapid application of 1-10 mM GABA elicited current responses in > 85% of the cells examined. The dose-response relationship pooled from nine progenitor cells was best fit by a logistic function of EC50=113 microM and Hill coefficient=0.9. In contrast to the rate of current deactivation, the rate of current activation exhibited marked concentration-dependence. Pharmacologically, GABA, muscimol and ZAPA ((Z)-3[(aminiiminomethyl)thio]prop-2-enoic acid sulphate) produced responses with ligand-specific kinetics, whereas glycine and the GABA(C) receptor agonist CACA were without effect; bicuculline methochloride acted as a competitive antagonist. Neither the amplitude nor the kinetics of currents produced by 100 microM GABA were affected by the benzodiazepine flunitrazepam (1 microM). Similarly the benzodiazepine receptor inverse agonist DMCM (1 microM) was also without effect. GABA-activated currents reversed polarity within 2 mV of the calculated Cl- equilibrium potential. With brief agonist pulses deactivation was monoexponential, however, unlike neurones the rate of deactivation was voltage-independent. Desensitisation of responses to 10 mM GABA was bi-exponential and accelerated at depolarised membrane potentials. Increasing the amount of GABA(A) receptor desensitisation (by increasing the duration of the agonist exposure) consistently produced a slowing of deactivation.
MRC Laboratory of Molecular Biology, Division of Neurobiology, Cambridge, UK.
A V
AV
Williamson
J R
JR
Mellor
A L
AL
Grant
A D
AD
Randall
D000179:Acrylates / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D018755:GABA Agonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000179:Acrylates; D018755:GABA Agonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C058552:3-((aminoiminomethyl)thio)-2-propenoic acid; C006749:bicuculline methochloride; D011188:Potassium; D001640:Bicuculline