Synchronized exocytotic bursts from gonadotropin-releasing hormone-expressing cells: Dual control by intrinsic cellular pulsatility and gap junctional communication

Periodic secretion of GnRH from the hypothalamus is the driving force for t he release of gonadotropic hormones from the pituitary, but the roles of in dividual neurons in the context of this pulse generator are not known. In t his study we used FM1-43 to monitor the membrane turnover associated with e xocytosis in single GT1-7 neurons and found an intrinsic secretory pulsatil ity (frequency, 1.4 +/- 0.1/h; pulse duration, 17.3 +/- 0.6 min) that, duri ng time in culture, became progressively synchronized among neighboring cel ls. Voltage-gated calcium channels and gap junctional communication each pl ayed major role in synchronized pulsatility. An I-type calcium channel; inh ibitor, nimodipine, abolished synchronized pulsatility. In addition, functi onal gap junction communication among adjacent cells was detected, but only under conditions where pulsatile synchronization was also observed, and th e gap junction inhibitor octanol abolished both without affecting pulse fre quency or duration. Our results, therefore, provide strong evidence that th e GnRH pulse generator in GT1-7 cells arises from a single cell oscillator mechanism that is synchronized through network signaling involving voltage- gated calcium channels and gap junctions.