Postnatal development of GABAB-receptor-mediated modulation of potassium currents in brainstem respiratory network of mouse.
The GABA(B)-receptor is known to activate a potassium conductance that is inwardly-rectifying, Ba(2+)-sensitive and mediated by G-protein-coupled mechanism. The network that generates respiratory rhythm is located in the brainstem and is modulated by GABA(B)-receptors. The present study investigated the mechanisms by which GABA(B)-receptor activation modulates respiratory rhythm and how these effects change during the first 2 weeks of postnatal development (P0-P15). Whole-cell patch clamp recordings were obtained from inspiratory neurons in the ventral respiratory column of acute brain stem slice of mouse. In presence of TTX and cadmium, application of baclofen, a GABA(B)-receptor agonist, activated an inwardly-rectifying potassium current. The reversal potential of the current was around -78 mV, which was close to the calculated equilibrium potential of potassium. The action of baclofen was dose-dependent and could be partially blocked (>85%) by a selective GABA(B)-receptor antagonist CGP 55845A. The current density of the baclofen-activated potassium currents increased over the first 2 postnatal weeks. At the cellular level, baclofen-activated potassium currents hyperpolarized inspiratory neurons in a concentration- and age-dependent manner. At the network level, the frequency of the respiratory rhythm decreased or was abolished depending on the concentration of baclofen applied. Our results indicate that the endogenous modulation of respiratory rhythm by GABA(B)-receptors that we have demonstrated previously is mediated at least in part through activation of an inwardly rectifying K(+) conductance and that this effect increases postnatally.
Pfeiffer
A
A
Center of Physiology and Pathophysiology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Zhang
W
W
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D018755:GABA Agonists / Q000494:pharmacology; D001239:Inhalation / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*
D018755:GABA Agonists; D024661:Potassium Channels, Inwardly Rectifying; D018080:Receptors, GABA-B; D001418:Baclofen