A store-operated current (SOC) mediates oxytocin autocontrol in the developing rat hypothalamus.
Oxytocin (OT) and vasopressin (VP) autocontrol their secreting neurons in the supraoptic nucleus (SON) by modulating action potential firing through activation of specific metabotropic receptors. However, the mechanisms linking receptor activation to firing remain unknown. In almost all cell types, activation of plasma membrane metabotropic receptors triggers signalling cascades that induce mobilization of calcium from intracellular stores. In turn, emptying the calcium stores may evoke calcium influx through store-operated channels (SOCs), the functions of which remain largely unknown in neurons. In this study, we show that these channels play a key role in the SON, at least in the response to OT. In isolated rat SON neurons, store depletion by thapsigargin induced an influx of calcium, demonstrating the presence of SOCs in these neurons. This calcium influx was specifically inhibited by 0.2 mM 1-(2-trifluoromethylphenyl-)imidazole (TRIM). At 2 mM, this compound affected neither the resting electrophysiological properties nor the voltage-dependant inward currents. In fresh slices, TRIM (2 mM) did not affect the resting potential of SON neurons, action potential characteristics, spontaneous action potential firing or synaptic activity; this compound thus appears to be a specific blocker of SOCs in SON neurons. TRIM (0.2 mM) specifically reduced the increase in action potential firing triggered by OT but did not affect the VP-induced response. These observations demonstrate that store operated channels exist in hypothalamic neurons and specifically mediate the response to OT in the SON.
Tobin
Vicky
V
Institut de Génomique fonctionnelle, CNRS UMR 5203, INSERM U661, University Montpellier I et II, 141 Rue de la Cardonille, 34094 Montpellier Cedex, France.
Gouty
Laurie-Anne
LA
Moos
Françoise C
FC
Desarménien
Michel G
MG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D009924:Organ Culture Techniques; D010121:Oxytocin / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D013495:Supraoptic Nucleus / Q000254:growth & development* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007093:Imidazoles; C098186:1-(2-trifluoromethylphenyl)imidazole; D010121:Oxytocin; D019284:Thapsigargin; D002118:Calcium