Baclofen: reduction of presynaptic calcium influx in the cat spinal cord in vivo.
In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, micro-electrophoretically administered (-)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (-)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (-)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (-)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (-)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (-)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (-)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (-)-baclofen and the different sensitivities of transmitter release at various central synapses.
Curtis
D R
DR
Division of Neuroscience, John Curtin School of Medical Research, Canberra, Australia.
Gynther
B D
BD
Lacey
G
G
Beattie
D T
DT
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002415:Cats; D005260:Female; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D001418:Baclofen; D002118:Calcium