Altered regulation of potassium and calcium channels by GABA(B) and adenosine receptors in hippocampal neurons from mice lacking Gα(o)

Gabriela J. Greif, Deborah L. Sodickson, Bruce P. Bean, Eva J. Neer, Ulrike Mende

    Research output: Contribution to journalArticlepeer-review

    Abstract

    To examine the role of G(o) in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of Gα(o). In CA3 neurons from Gα(o)/(-/-) mice, 2-chloro-adenosine and the GABA(B)-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited voltage-dependent Ca2+ currents just as effectively as in Gα(o)/(+/+) littermates. However, the kinetics of transmitter action were dramatically altered in Gα(o)/(-/-) mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from Gα(o)/(-/-) mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from Gα(o)/(+/+) mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2- chloroadenosine on Ca2+ currents and K+ currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking Gα(o), some inhibition of Ca2+ currents by baclofen remained after NEM treatment, whereas baclofen activation of K+ currents and both effects of 2-chloro- adenosine were abolished. These results show that modulation of Ca2+ and K+ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for Gα(o). However, modulation is changed in the absence of Gα(o) in having much slower recovery kinetics. A likely possibility is that the very abundant Gα(o) is normally used but, when absent, can readily be replaced by G proteins with different properties.

    Original languageEnglish (US)
    Pages (from-to)1010-1018
    Number of pages9
    JournalJournal of neurophysiology
    Volume83
    Issue number2
    DOIs
    StatePublished - 2000

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Physiology

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