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Actions of the GABA B agonist, (−)‐baclofen, on neurones in deep dorsal horn of the rat spinal cord in vitro
Author(s) -
Allerton C.A.,
Boden P.R.,
Hill R.G.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11780.x
Subject(s) - baclofen , postsynaptic potential , excitatory postsynaptic potential , chemistry , inhibitory postsynaptic potential , spinal cord , gabab receptor , neuroscience , agonist , pharmacology , biophysics , medicine , biochemistry , biology , receptor
1 The electrophysiological actions of the GABA B agonist, (−)‐baclofen, on deep dorsal horn neurones were studied using an in vitro preparation of the spinal cord of 9–16 day old rat. 2 On all neurones tested, (−)‐baclofen (100nM‐30μ m ) had a hyperpolarizing action which was associated with a reduction in apparent membrane input resistance. The increase in membrane conductance was dose‐dependent and had a Hill coefficient of 1.0. 3 The (−)‐baclofen‐activated hyperpolarization persisted in the presence of bicuculline (50 μ m ) and Mg 2+ (20 m m ). 4 The reversal potential of the hyperpolarizing event was estimated at 102 mV and was made less negative by increasing the external concentration of potassium ions. 5 Over the same concentration range, (−)‐baclofen also depressed the polysynaptic composite excitatory postsynaptic potentials (e.p.s.ps) evoked in these neurones by electrical stimulation of the dorsal root entry zone. 6 The potassium channel blockers caesium, applied intracellularly, and barium, applied extracellularly, depressed the postsynaptic response to baclofen but not its effect on e.p.s.ps. 7 We propose that (−)‐baclofen has more than one mechanism of action in spinal dorsal horn: a postsynaptic action mediated via an increase in potassium conductance and a presynaptic action that is not associated with potassium channels and may be mediated via calcium channels. Since previous studies have demonstrated little effect of (−)‐baclofen on transmitter release in spinal cord, it is possible that the postsynaptic hyperpolarizing action of (−)‐baclofen may account for its clinical potency as an anti‐spastic agent.