Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular recordings were made from neurons in rat dorsal raphe in the slice preparation maintained at 37 degrees C. The single-electrode voltage-clamp method was used to measure membrane currents at potentials more negative than rest (-60 mV). Three types of inward rectification were observed: 2 in the absence of any drugs and the third induced by 5-HT 1 and GABA-B receptor agonists. In the absence of any drugs, an inward current activated over 1-2 sec when the membrane potential was stepped to potentials more negative than -70 mV. This current was blocked by cesium (2 mM) and resembles IQ or IH. A second inward current (IIR) occurred at membrane potentials near the potassium equilibrium potential (EK). This inward current activated within the settling time of the clamp and was abolished by both barium (10-100 microM) and cesium (2 mM). 5-HT 1 agonists activated a potassium conductance that hyperpolarized the cells at rest. This potassium conductance was about 2 nS at -60 mV and increased linearly with membrane hyperpolarization to about 4 nS at -120 mV. Baclofen activated a potassium conductance identical in amplitude and voltage dependence to that induced by 5-HT 1 agonists. Both the baclofen- and 5-HT-induced currents were nearly abolished in animals pretreated with pertussis toxin. The results indicate that a common potassium conductance is increased by 5-HT acting on 5-HT 1 receptors and baclofen acting on GABA-B receptors. This potassium conductance rectifies inwardly and is distinct from the Q-current. The ligand-activated potassium conductance also differs from the other form of inward rectification (IIR) in its voltage dependence and sensitivity to pertussis toxin.
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PMID:Voltage- and ligand-activated inwardly rectifying currents in dorsal raphe neurons in vitro. 317 86

We studied the effects of GABA on anoxia-induced injury in CNS white matter using optic nerves exposed to 60 min of anoxia. Injury was assessed by recording pre- and postanoxic compound action potentials (CAPs). GABA (1 microM) significantly increased postanoxic CAP recovery when applied 60 min prior to anoxia. This effect was bicuculline (100 microM) insensitive, mimicked by baclofen (1 microM), blocked by GABA-B antagonists, and not mimicked by selective GABA-A agonists. GABA therefore acted at GABA-B receptors. High concentrations of GABA and baclofen did not influence recovery, possibly indicating GABA-B receptor desensitization at high agonist concentrations. Pertussis toxin (PTX) treatment reduced postanoxic CAP recovery in the presence of 1 microM GABA to control levels, indicating the recruitment of a G-protein-linked intracellular pathway. Protein kinase C (PKC) activation with 12-myristate 13-acetate (PMA) mimicked the effects of GABA. Inhibition of PKC with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) or staurosporine reduced postanoxic recovery in the presence of GABA to lower levels than under control conditions, confirming the involvement of PKC in the protective effect of GABA and indicating that this GABA-B receptor/G-protein/PKC protective pathway might be active under control conditions. This was confirmed by the observation that GABA-B receptor blockade, in the absence of exogenous GABA, significantly reduced postanoxia recovery. Thus, activation of the protective mechanism under control conditions is due to endogenous GABA release. Increasing the level of endogenous extracellular GABA by blocking GABA uptake with 1 mM nipecotic acid also protected against anoxia. We propose a model where release of GABA in white matter helps to limit nerve fiber injury during anoxia via recruitment of a G-protein/PKC pathway with subsequent phosphorylation of an unknown target protein.
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PMID:Endogenous GABA attenuates CNS white matter dysfunction following anoxia. 782 73