GABA(B) receptor-activated inwardly rectifying potassium current in dissociated hippocampal CA3 neurons

Deborah L. Sodickson, Bruce P. Bean

    Research output: Contribution to journalArticlepeer-review

    Abstract

    GABA and the GABA(B) receptor agonist baclofen activated a potassium conductance in acutely dissociated hippocampal CA3 neurons. Baclofen- activated current required internal GTP, was purely potassium selective, and showed strong inward rectification. As with acetylcholine-activated current in atrial myocytes, external Cs+ blocked inward but not outward current in a highly voltage-dependent manner, whereas Ba2+ blocked with no voltage dependence. Unlike the cardiac current, however, the baclofen-activated current showed no intrinsic voltage-dependent relaxation. With fast solution exchange, current was activated by baclofen or GABA with a lag of ~50 msec followed by an exponential phase (time constant ~225 msec at saturating agonist concentrations); deactivation was preceded by a lag of ~150 msec and occurred with a time constant of ~1 sec. GABA activated the potassium conductance with a half maximally effective concentration (EC50) of 1.6 μM, much lower than that for activation of GABA(A) receptor-activated chloride current in the same cells (EC50 ~25 μM). At low GABA concentrations, activation of the GABA(B) current had a Hill coefficient of 1.4-2.1, suggesting cooperativity in the receptor-to-channel pathway. Although the maximal conductance activated by GABA(B) receptors is much smaller than that activated by GABA(A) receptors, its higher sensitivity to GABA and slower time course make it well suited to respond to low concentrations of extra-synaptic GABA.

    Original languageEnglish (US)
    Pages (from-to)6374-6385
    Number of pages12
    JournalJournal of Neuroscience
    Volume16
    Issue number20
    DOIs
    StatePublished - Oct 15 1996

    Keywords

    • G-protein
    • GABA
    • GABA(A)
    • GIRK
    • baclofen
    • barium
    • cesium
    • chloride current

    ASJC Scopus subject areas

    • Neuroscience(all)

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