Mechanisms of Spontaneous Calcium oscillations in GnRH neurons

The gonadotropin-releasing hormone (GnRH) neurosecretory system constitutes the final common pathway in the neuroendocrine control of reproduction. However, the mechanisms of pulsatile and cyclic GnRH release remain poorly understood. To understand the synchronous GnRH neuron activity, which may be base of pulsatile and cyclic GnRH release, we monitored intracellular Ca²⁺ oscillations in GT1-7 cells and native GnRH neurons. Removal of extracellular Ca²⁺ abolished Ca²⁺ oscillations, whereas thapsigargin (inhibitor of ER Ca²⁺-ATPase) had no effect. Nifedipine (L-type Ca²⁺ channel blocker), SNX-482 (R-type blocker) and ω-conotoxin-GVIA (N-type blocker) abolished Ca²⁺ oscillations, indicated that Ca²⁺ oscillations was brought by an influx of Ca²⁺ through the voltage-gated Ca²⁺ channels. GnRH receptor (G-protein coupled receptor) antagonist abolished Ca²⁺ oscillations, suggested that Ca²⁺ oscillations were modulated by GnRH autocrine. Pertussis toxin enhanced Ca²⁺ oscillations, whereas H-89 (protein kinase A inhibitor) abolished Ca²⁺ oscillations. A high [K⁺]_o enhanced Ca²⁺ oscillations in frequency and TTX (voltage-gated Na⁺ channel blocker) abolished Ca²⁺ oscillations. TEA and 4AP (voltage-gated K⁺ channel blocker) enhanced Ca²⁺ oscillations. These results suggest that Ca²⁺ oscillations in GnRH neurons are mediated by voltage-gated K⁺ channel activity affected by GnRH receptor and pertussis toxin -sensitive G protein. [J Physiol Sci. 2008;58 Suppl:S140]