Guanine nucleotide binding proteins mediate D2 dopamine receptor activation of a potassium channel in rat lactotrophs

L. C. Einhorn, G. S. Oxford

Research output: Contribution to journalArticle

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Abstract

The involvement of guanine nucleotide binding proteins in the coupling of D2 dopamine (DA) receptors to single potassium channels was examined in rat pituitary lactotrophs. Lactotrophs were unambiguously identified by the reverse haemolytic plaque assay (RHPA) and membrane potentials, whole-cell and single channel currents recorded using patch electrode methods. DA or the D2 selective agonist, quinpirole, induced the opening of single K+ channels in cell-attached patches underlying robust hyperpolarizations of membrane potential in single cells. Both whole-cell and single channel responses were independent of Ca2+ or cAMP concentrations. Pertussis toxin (PTX) pretreatment (50-250 ng/ml, 6-12 h) blocked the action of DA on lactotroph membrane potential and uncoupled D2 receptors from single K+ channels in cell-attached patches. Internal dialysis with GDPβS (guanosine 5'-O-(2-thiodiphosphate) greatly reduced whole-cell responses to DA in a dose-dependent manner. Internal dialysis of lactotrophs with GTPγS (guanosine 5'-O-(3-thiotriphosphate) potentiated DA responses in a dose-dependent manner while rendering the responses irreversible at higher doses. DA (100 nM) or quinpirole (10 μM) activated K+ channels in excised outside-out membrane patches that were identical to those identified in cell-attached patches in terms of conductance and gating kinetics. It is proposed that D2 receptors are coupled to non-voltage-dependent K+ channels by G proteins of the G(i)/G(o) class and that this coupling is via a direct, membrane delimited pathway.

Original languageEnglish (US)
Pages (from-to)563-578
Number of pages16
JournalJournal of Physiology
Volume462
StatePublished - 1993
Externally publishedYes

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Lactotrophs
Guanine Nucleotides
Dopamine D2 Receptors
Potassium Channels
Carrier Proteins
Dopamine
Membrane Potentials
Quinpirole
Dialysis
Guanosine 5'-O-(3-Thiotriphosphate)
Membranes
Pertussis Toxin
GTP-Binding Proteins
Electrodes

ASJC Scopus subject areas

  • Physiology

Cite this

Guanine nucleotide binding proteins mediate D2 dopamine receptor activation of a potassium channel in rat lactotrophs. / Einhorn, L. C.; Oxford, G. S.

In: Journal of Physiology, Vol. 462, 1993, p. 563-578.

Research output: Contribution to journalArticle

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