Purkinje cell inhibitory responses to 3-APPA (3-aminopropylphosphinic acid) in RAT cerebellar slices.
3-APPA is considered to be a GABA(B) agonist more potent than baclofen. We report here the results obtained by applying this agonist to Purkinje cells (PCs) recorded in current clamp mode on cerebellar slices. The responses were compared to those obtained with other GABA agonists and antagonists. The drugs were delivered either in the perfusion solution or by pressure to the molecular layer near the recorded cell. When applied to the PCs either in the bathing medium or by pressure, 3-APPA evoked a potent inhibitory response which was however different from that obtained with baclofen. The response was complex and similar to that evoked by application of GABA, the endogenous neurotransmitter. In fact it showed: (1) very sensitive dose-response not affected by TTX in the bath; (2) an equilibrium potential compatible with Cl-channel conductance; (3) a massive reduction with the competitive GABA(A) antagonist bicuculline; (4) a small reduction, if any, with the potent competitive GABA(B) antagonist CGP55845A; (5) persistence of the responses under 4-AP (4-aminopyridine), the potassium channel blocker, and inhibition of the 4-AP-induced calcium bursts of spikes. The conclusion was reached that the inhibitory response of PCs to 3-APPA is induced, like GABA inhibition, by binding to both GABA(A) and GABA(B) postsynaptic receptors.
Vigot
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Laboratoire de Physiologie de la Motricité, CNRS UMR 9923, Université Pierre et Marie Curie, CHU Pitié-Salpêtrière, Paris, France.
Batini
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D015761:4-Aminopyridine / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D011412:Propanolamines; C061388:3-aminopropylphosphinic acid; C085075:CGP 55845A; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015761:4-Aminopyridine; D001418:Baclofen; D001640:Bicuculline