The role of GABAA and GABAB receptors in presynaptic inhibition of Ia EPSPs in cat spinal motoneurones.
1. The role of GABAA and GABAB receptors in presynaptic inhibition was studied by examining the effect of local application of antagonists by ionophoresis during intracellular recording of presynaptic inhibition of compound and unitary group Ia afferent excitatory postsynaptic potentials (EPSPs) in gastrocnemius motoneurones. 2. Ionophoresis of the GABAA antagonist bicuculline methochloride (BMC) was found to block presynaptic inhibition of both compound and unitary EPSPs by up to 85%. BMC also substantially reduced, and occasionally abolished, the late part of the inhibitory postsynaptic potential (IPSP) evoked in motoneurones by the conditioning stimulation. The early part of this IPSP was found to be sensitive to ionophoresis of strychnine hydrochloride. 3. Ionophoresis of 2-OH-saclofen caused a reduction in presynaptic inhibition of compound EPSPs by 5-25% but had no effect on the IPSP evoked in motoneurones by the conditioning stimulation. 4. Ionophoresis of the GABAB antagonist (-)-baclofen reduced the amplitude of unconditioned EPSPs; however it had little effect on presynaptic inhibition. 5. It was concluded that at the Ia afferent-motoneurone synapse presynaptic inhibition is mediated primarily through the activation of GABAA receptors. The activation of GABAB receptors appears to play only a minor role in presynaptic inhibition at this synapse. This contrasts with the relative ease with which (-)-baclofen can reduce transmitter release from Ia afferent terminals and suggests that the receptors activated by (-)-baclofen are predominantly extrasynaptic.
Stuart
G J
GJ
Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra.
Redman
S J
SJ
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002415:Cats; D005071:Evoked Potentials / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D001418:Baclofen; C006749:bicuculline methochloride; C057491:2-hydroxysaclofen; D001640:Bicuculline