36Cl- flux measurements on GABAA receptor-activated chloride exchange. Multiple mechanisms of the chloride channel inactivation.
The technique of radiotracer 36Cl- influx in primary culture of rat cerebellar granule cells was applied to study the mechanism of inactivation of the GABAA receptor-activated chloride channel. During sustained application of GABA, muscimol and THIP the specific bicuculline-sensitive 36Cl- influx tends to decline with time. The sequence in decay half-time is GABA less than muscimol less than THIP. Diazepam accelerates the rate of decay of the peak response to GABA. (-)-Baclofen enhances the rate of decline of the response to muscimol in a dose-dependent manner. Treatment of the cells with pertussis toxin antagonized the effect of (-)-baclofen. It is concluded that rat neonatal cerebellar neurons maintained in tissue culture exhibit complex inactivation of the GABAA channel, indicating some interaction with the GABAB receptor system.
Kardos
J
J
Central Research Institute for Chemistry, Hungarian Academy of Sciences.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002531:Cerebellum / Q000378:metabolism; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D002713:Chlorine / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D037342:Pertussis Toxin; D011868:Radioisotopes; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011868:Radioisotopes; D011963:Receptors, GABA-A; D010566:Virulence Factors, Bordetella; D009118:Muscimol; D002713:Chlorine; D037342:Pertussis Toxin; D001418:Baclofen; D003975:Diazepam