Activation of type B gamma-aminobutyric acid receptors in the intact mammalian spinal cord mimics the effects of reduced presynaptic Ca2+ influx.
Intracellular recordings from mammalian spinal motoneurons in vivo show that the type B gamma-aminobutyric acid receptor agonist, L-(-)-baclofen, when administered systemically to pentobarbital-anesthetized or decerebrate unanesthetized cats decreases the amplitude of monosynaptic group Ia excitatory postsynaptic potentials (EPSPs), markedly increases tetanic and posttetanic potentiation, and reduces or abolishes synaptic depression during high-frequency synaptic activation and in the posttetanic period. These changes occur without detectable alteration in motoneuron input resistance, EPSP shape, or the invasion of action potentials into the intraspinal group Ia terminal arborizations. The baclofen-induced effects are qualitatively similar to those observed in more accessible synaptic systems when presynaptic Ca2+ influx and, concomitantly, transmitter release are reduced. Based on these and other recent findings regarding the mechanism of action of baclofen and the distribution of its receptors in the spinal cord, we suggest that L-(-)-baclofen modifies frequency modulation of Ia synaptic transmission by reducing presynaptic Ca2+ influx and the concomitant level of transmitter release from Ia afferent terminals. The drug appears to be a useful tool in studies of the ionic mechanisms that control the release of transmitter and its frequency modulation at inaccessible mammalian synapses.
Lev-Tov
A
A
Laboratory of Neural Control, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Meyers
D E
DE
Burke
R E
RE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009046:Motor Neurons / Q000502:physiology; D009119:Muscle Contraction; D009132:Muscles / Q000294:innervation / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D011963:Receptors, GABA-A; D001418:Baclofen; D002118:Calcium