Modulation of ion channels underlying excitation-secretion coupling in identified lactotrophs and gonadotrophs.
The role of ion channel activity in the response of rat pituitary lactotrophs and gonadotrophs to dopamine (DA) and GnRH, respectively, was investigated. Single lactotrophs and gonadotrophs were unambiguously identified with the reverse hemolytic plaque assay, and recordings of membrane potential and current were obtained using whole-cell and single-channel patch-clamp techniques. In lactotrophs, DA inhibited spontaneous electrical activity by activating a K+ conductance that hyperpolarized the cells. A 50 pS K+ channel underlies this response and was activated following agonist binding to a D2 type receptor via a "direct" interaction with a pertussis toxin-sensitive G-protein. In gonadotrophs, GnRH triggers rhythmic hyperpolarizations due also to a K+ conductance increase. The K+ channel underlying the GnRH response is an apamin-sensitive, Ca(2+)-activated channel. Although both agonists produce hyperpolarizations in their respective target cells via K+ channel activation, differences in intracellular calcium response probably discriminate the stimulatory (GnRH) and inhibitory (DA) actions on hormone secretion. Each K+ channel type plays a different role in modulating the intracellular Ca2+ levels to yield these actions.
Oxford
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Department of Physiology, University of North Carolina, Chapel Hill 27599.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007473:Ion Channels; D015221:Potassium Channels; D007987:Gonadotropin-Releasing Hormone; D015544:Inositol 1,4,5-Trisphosphate; D011388:Prolactin; D007986:Luteinizing Hormone; D002118:Calcium; D004298:Dopamine