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

LC Einhorn, KA Gregerson and GS Oxford
Journal of Neuroscience 1 December 1991, 11 (12) 3727-3737; https://doi.org/10.1523/JNEUROSCI.11-12-03727.1991
LC Einhorn
University of North Carolina, Chapel Hill 27599.
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KA Gregerson
University of North Carolina, Chapel Hill 27599.
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GS Oxford
University of North Carolina, Chapel Hill 27599.
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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 microM) 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 microM). 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 microM). 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.

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The Journal of Neuroscience: 11 (12)
Journal of Neuroscience
Vol. 11, Issue 12
1 Dec 1991
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D2 dopamine receptor activation of potassium channels in identified rat lactotrophs: whole-cell and single-channel recording
LC Einhorn, KA Gregerson, GS Oxford
Journal of Neuroscience 1 December 1991, 11 (12) 3727-3737; DOI: 10.1523/JNEUROSCI.11-12-03727.1991

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D2 dopamine receptor activation of potassium channels in identified rat lactotrophs: whole-cell and single-channel recording
LC Einhorn, KA Gregerson, GS Oxford
Journal of Neuroscience 1 December 1991, 11 (12) 3727-3737; DOI: 10.1523/JNEUROSCI.11-12-03727.1991
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