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 wi th pentobarbitone sodium, microelectrophoretically administered (-)-ba clofen, but not (+)-baclofen, reversibly reduced the duration of the o rthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presum ably submicromolar concentrations are already known to reversibly redu ce excitatory transmitter release from muscle group Ia afferent termin ations. Action potential durations were estimated from threshold recov ery curves after an orthodromic impulse using an extracellular microst imulation technique. Both of these presynaptic effects of (-)-baclofen were blocked by baclofen antagonists, and neither appeared to be redu ced by the potassium channel blocking agents tetraethylammonium and 4- aminopyridine. Tetraethylammonium and 4-aminopyridine also did not sig nificantly modify the reduction by (-)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbiton e sodium. In the cat the maximum reduction by (-)-baclofen of terminat ion action potentials was considerably less than that produced by cadm ium ions, which, unlike (-)-baclofen, also reduced the action potentia l duration of group I myelinated fibres. These findings are consistent with a reduction by (-)-baclofen of the influx of calcium through vol tage-activated channels in the membrane of group Ia terminations, a pr oposal which also accounts for the reduction by (-)-baclofen of the re lease of GABA at axo-axonic depolarizing synapses on these termination s. The results are discussed in relation to the mode of action of (-)- baclofen and the different sensitivities of transmitter release at var ious central synapses.