ACTIVATION OF GABA(B) RECEPTORS INCREASES A POTASSIUM CONDUCTANCE IN RAT BULBOSPINAL NEURONS OF THE C1 AREA

In anesthetized rats, iontophoresis of the gamma-aminobutyric acid (GA BA(B))-receptor agonist and antispastic drug baclofen inhibits the bul bospinal vasomotor neurons of the rostral ventrolateral medulla (RVLM) . The present study was carried out to determine whether C1 adrenergic and other bulbospinal neurons of the RVLM have postsynaptic GABAB rec eptors. Retrogradely labeled RVLM bulbospinal neurons (n = 52) were re corded in 120-mu m-thick slices from neonatal rat brain (3-10 days old ). Most neurons (48/52) were tonically active (3 +/- 0.6 spikes/s). Tw enty-six neurons were recovered histologically, and 18 of them were im munoreactive for tyrosine hydroxylase (TH). In current clamp, baclofen (0.3-10 mu M) hyperpolarized RVLM bulbospinal cells in a dose-depende nt manner (16 +/- 0.5 mV hyperpolarization by 3 mu M baclofen; n = 19) and decreased input resistance by 40% (n = 10). In voltage clamp (1 m u M tetrodotoxin present; holding potential: -40 to -60 mV), 3 PM bacl ofen induced an outward current of 21 +/- 2 pA (n = 29). This current exhibited inward rectification and reversed polarity close to the K+ e quilibrium potential (external K+ from 2.5 to 10 mM). The current indu ced by baclofen was reduced 90% by 0.1-0.2 mM BaCl2 (n = 6) and was bl ocked reversibly by the selective GABA(B)-receptor antagonist CGP-5584 5A (0.5-1 mu M; n = 6). All histologically verified TH-immunoreactive cells (n = 18) were sensitive to baclofen. In summary, RVLM bulbospina l neurons including C1 adrenergic cells possess GABAB receptors. Activ ation of these receptors increases an inwardly rectifying K+ conductan ce. This effect reduces the intrinsic firing frequency of RVLM vasomot or neurons ''in vitro'' and may contribute to the sympatholytic action of baclofen ''in vivo.