D2 dopamine receptor activation of potassium channels in identified rat lactotrophs: Whole-cell and single-channel recording

L. C. Einhorn, K. A. Gregerson, G. S. Oxford

Research output: Contribution to journalArticle

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Abstract

Dopamine (DA) is the major physiological regulator of prolactin secretion from the anterior pituitary, exerting a tonic inhibitory control that is mediated by D2 DA receptors. D2 receptors in both the anterior pituitary and CNS are thought to produce some of their inhibitory effects via a coupling to potassium (K+) channels to increase K+ conductance. Utilizing the reverse hemolytic plaque assay and patch-clamp techniques, we characterize the actions of DA on membrane potential and associated DA-activated whole-cell current, as well as the single K+ channels that underlie the response in primary rat lactotrophs. We demonstrate that DA (5 nM to 1 μM) or D2-selective agonists (RU24213 and quinpirole) evoke a hyperpolarization of membrane potential that was blocked by D2 antagonists and associated with an increased K+ conductance. Whole-cell current responses to ramp voltage commands revealed a DA-activated current whose reversal potential was near the calculated Nernst potential for K+, varied as a function of K+ concentration, exhibited some inward rectification, and was Ca2+ independent. The current was insensitive to tetraethylammonium (TEA; 10 mM), partially blocked by 4-aminopyridine (4-AP; 5 mM), and almost completely inhibited by quinine (100 μM). Cell-attached recordings in the presence of DA or a D2 agonist revealed the opening of a K+ channel that was not present in the absence of DA or when a D2 receptor antagonist was included with DA. Analysis of the single-channel current showed the current-voltage relationship to be linear at negative patch potentials and yielded a unitary conductance of 40.2 pS in the presence of 150 mM KCl. The channels were not blocked by TEA (10 mM), were slightly suppressed by 4-AP (5 mM), and were almost completely inhibited by quinine (100 μM). These experiments establish that in primary rat lactotrophs, DA acts at D2 receptors to activate the opening of single K+ channels, which results in an increase in K+ conductance and associated membrane hyperpolarization. This is the first characterization of single DA-activated K+ channels in an endocrine cell.

Original languageEnglish (US)
Pages (from-to)3727-3737
Number of pages11
JournalJournal of Neuroscience
Volume11
Issue number12
StatePublished - 1991
Externally publishedYes

Fingerprint

Lactotrophs
Dopamine D2 Receptors
Potassium Channels
Dopamine
Quinine
Membrane Potentials
Quinpirole
4-Aminopyridine
Architectural Accessibility
Tetraethylammonium
Endocrine Cells
Patch-Clamp Techniques
Prolactin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

D2 dopamine receptor activation of potassium channels in identified rat lactotrophs : Whole-cell and single-channel recording. / Einhorn, L. C.; Gregerson, K. A.; Oxford, G. S.

In: Journal of Neuroscience, Vol. 11, No. 12, 1991, p. 3727-3737.

Research output: Contribution to journalArticle

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