Carbachol reduces IK,baclofen, but not IK,GABA in guinea pig hippocampal slices.

In the presence of bicuculline and/or picrotoxin (-)-baclofen and gamma-aminobutyric acid (GABA) induced outward currents (IBac and IGABA) at holding potentials of -55 to -75 mV in guinea pig CA3 neurones of hippocampal slices. Zero potentials for these currents were at the K-equilibrium potential indicating that they were carried by K-ions (IK.Bac, IK.GABA). IK.Bac was strongly reduced by carbachol (Cch) in low concentration (0.1 0.3 microM), while IK.GABA was not affected by Cch concentrations even up to 20 microM. The K-dependent late inhibitory postsynaptic potential (IPSP) was reduced significantly by Cch concentrations higher than 1 microM, but with these concentrations the early, Cl-dependent IPSP was reduced as well. The baclofen-derivative phaclofen, considered a selective antagonist of both the postsynaptic action of baclofen and the bicuculline - and picrotoxin - resistant action of GABA, exhibited, in our hands, partial agonistic effects and effects on non-transmitter gated K-currents. Our findings cast some doubt on the assumption that IK.Bac, IK.GABA and the late IPSP are all mediated by the same receptor and generated by the same mechanism.