Long-term GABAA receptor activation increases [Ca2+]i in single lactotrophs.
Prolactin (PRL) release by pituitary lactotrophs is inhibited by gamma-aminobutyric acid (GABA). We have investigated the effect of long-lasting activation of GABAA receptors on membrane potential and cytosolic free calcium concentration ([Ca2+]i) in single identified lactotrophs. Membrane potential was recorded using the perforated patch-clamp technique and [Ca2+]i using indo 1 as a fluorescent Ca2+ probe. When cells were bathed in muscimol (10 microM) for 30 min, [Ca2+]i unexpectedly increased in 53% of the lactotrophs. This was due to a Ca2+ influx, since it was inhibited by Ca(2+)-free extracellular medium or by Ca2+ channel blockers such as the dihydropyridine PN 200-110. In cells incubated in muscimol, wash of muscimol from the cell membrane potential and reduced [Ca2+]i to the levels found in control cells. This effect was mimicked by picrotoxin, a GABA-operated Cl- channel blocker, thus supporting the involvement of a muscimol-induced Cl- flux. Conversely, under similar experimental conditions, static assays of PRL release revealed an inhibition of release by muscimol, unaffected by the dihydropyridine PN 200-110. Our observations suggest that GABAA, receptors may not regulate the process of exocytosis within the Ca(2+)- regulated steps.
Lorsignol
A
A
Laboratoire de Neurophysiologie, Centre National de la Recherche Scientifique Unité de Recherche Associée 1200, Université de Bordeaux II, France.
Taupignon
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A
Dufy
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D058785:GABA-A Receptor Agonists; D009118:Muscimol / Q000494:pharmacology; D009994:Osmolar Concentration; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D013997:Time Factors
D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D011388:Prolactin; D002118:Calcium