Activation of GABAB receptors increases a potassium conductance in rat bulbospinal neurons of the C1 area.
In anesthetized rats, iontophoresis of the gamma-aminobutyric acid (GABAB)-receptor agonist and antispastic drug baclofen inhibits the bulbospinal 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 receptors. Retrogradely labeled RVLM bulbospinal neurons (n = 52) were recorded in 120-micron-thick slices from neonatal rat brain (3-10 days old). Most neurons (48/52) were tonically active (3 +/- 0.6 spikes/s). Twenty-six neurons were recovered histologically, and 18 of them were immunoreactive for tyrosine hydroxylase (TH). In current clamp, baclofen (0.3-10 microM) hyperpolarized RVLM bulbospinal cells in a dose-dependent manner (16 +/- 0.5 mV hyperpolarization by 3 microM baclofen; n = 19) and decreased input resistance by 40% (n = 10). In voltage clamp (1 microM tetrodotoxin present; holding potential: -40 to -60 mV), 3 microM baclofen induced an outward current of 21 +/- 2 pA (n = 29). This current exhibited inward rectification and reversed polarity close to the K+ equilibrium potential (external K+ from 2.5 to 10 mM). The current induced by baclofen was reduced 90% by 0.1-0.2 mM BaCl2 (n = 6) and was blocked reversibly by the selective GABAB-receptor antagonist CGP-55845A (0.5-1 microM; n = 6). All histologically verified TH-immunoreactive cells (n = 18) were sensitive to baclofen. In summary, RVLM bulbospinal neurons including C1 adrenergic cells possess GABAB receptors. Activation of these receptors increases an inwardly rectifying K+ conductance. This effect reduces the intrinsic firing frequency of RVLM vasomotor neurons "in vitro" and may contribute to the sympatholytic action of baclofen "in vivo."
Li
Y W
YW
Department of Pharmacology, University of Virginia, Charlottesville 22908, USA.
Guyenet
P G
PG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004553:Electric Conductivity; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010721:Phosphinic Acids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D017609:Barium Compounds; D002712:Chlorides; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011412:Propanolamines; D018080:Receptors, GABA-B; C024986:barium chloride; C085075:CGP 55845A; D014446:Tyrosine 3-Monooxygenase; D001418:Baclofen; D011188:Potassium