title: Baclofen increases the potassium conductance of rat locus coeruleus neurons recorded in brain slices.
abstract: Baclofen causes a concentration-dependent inhibition of spontaneous firing, hyperpolarization and resistance decrease in locus coeruleus (LC) neurons recorded intracellularly in a brain slice preparation. The (-) isomer is active while the (+) isomer has little or no activity which indicates that the baclofen effect is stereoselective. Baclofen action on LC neurons is a direct postsynaptic effect since it remains in low Ca2+, high Mg2+ media. Baclofen actions on LC neurons are resistant to the GABAA antagonist bicuculline. The baclofen-induced hyperpolarization reverses at the K+ equilibrium potential, as estimated by the reversal potential of the post-stimulus hyperpolarization which follows an evoked train of action potentials. When the K+ concentration in the superfusion media is increased, the reversal potential for the baclofen-induced hyperpolarization shifts linearly with a slope of 61 mV per 10-fold change as predicted by the Nernst equation for a pure K+ conductance. The baclofen-induced K+ conductance increase is prevented by addition of the K+-channel blocker Ba2+ to the external media. Taken together, these data suggest that baclofen directly hyperpolarizes LC neurons by activation of GABAB receptors which leads to an increase in K+ conductance.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois, College of Medicine, Chicago 60612.
authors.forename: S S
authors.initials: SS
authors.lastname: Osmanović
authors.forename: S A
authors.initials: SA
authors.lastname: Shefner
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D066298:In Vitro Techniques; D007536:Isomerism; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011188:Potassium / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
chemical_list: D002413:Cations, Divalent; D011963:Receptors, GABA-A; D001418:Baclofen; D011188:Potassium