Baclofen reduces post-synaptic potentials of rat cortical neurones by an action other than its hyperpolarizing action

1. Intracellular recordings were obtained from neurones in layers 2
and 3 of the rat frontal neocortex in an in vitro slice
preparation. Three distinct types of stimulation-evoked
post-synaptic potentials were recorded in these neurones:
excitatory post-synaptic potentials (e.p.s.p.s);
bicuculline-sensitive, chloride-dependent inhibitory post-synaptic
potentials (i.p.s.p.s) with times to peak of 20-25 ms
(fast(f)-i.p.s.p.s); bicuculline-insensitive, potassium-dependent
i.p.s.p.s with bicuculline-insensitive, potassium-dependent
i.p.s.p.s with times to peak of 150-250 ms (long(l)-i.p.s.p.s). 2.
The effects of baclofen were investigated on seventy-one neurones.
Baclofen was applied by ionophoresis or pressure ejection from
micropipettes or was added to the superfusion medium. 3. Baclofen
depressed stimulation-evoked e.p.s.p.s in fifty-seven of the sixty
neurones tested. This effect was associated with an increase in the
stimulation intensity required to produce a synaptically evoked
action potential for thirty-nine of forty-four neurones. 4.
Baclofen depressed f-i.p.s.p.s in thirty-seven of the thirty-nine
neurones tested and l-i.p.s.p.s in each one of the seventeen
neurones tested. Reversal potential values for each type of
i.p.s.p. were not changed by baclofen and its depressions of each
were independent of membrane potential (Em). Baclofen reduced the
magnitude and the duration of the conductance increases that were
associated with f- and l-i.p.s.p.s. 5. Baclofen hyperpolarized
forty of seventy-one neurones and produced outward currents in
three of four neurones recorded in voltage clamp at holding
potentials between -55 and -65 mV. These actions were associated
with 10-58% reductions of neuronal input resistance (RN) and 10-20%
increases in neuronal input conductance (gN), respectively.
Baclofen decreased the direct excitability of twenty-three of
twenty-seven neurones tested. Determinations of the reversal
potential for baclofen-induced changes of Em indicate that baclofen
increases the conductance of rat neocortical neurones to potassium
ions. 6. The EC50 for each action of DL-baclofen was approximately
1 microM. L-Baclofen was greater than 100 times more potent than
D-baclofen. 7. Concentrations of bicuculline that blocked
f-i.p.s.p.s and responses to ionophoretically applied
gamma-aminobutyric acid (GABA) had no effect on the depressions of
e.p.s.p.s or the hyperpolarizations and decreases in RN that
baclofen produced. 8. Baclofen did not reduce the duration of
action potentials that were prolonged with intracellular injections
of caesium ions or by superfusions with medium that contained 10
mM-tetraethylammonium (TEA).