Recovery of Ins(1,4,5)-trisphosphate-dependent calcium signaling in neonatal gonadotrophs.
Pituitary gonadotrophs express non-desensitizing gonadotropin-releasing hormone (GnRH) receptors and their activations leads to inositol 1,4,5-trisphosphate (InsP3)-dependent Ca2+ mobilization. When added in physiological concentration range GnRH induces baseline Ca2+ oscillations, whereas in higher concentrations it induces a prolonged spike response accompanied with non-oscillatory or oscillatory plateau response. Here, we studied the recovery of calcium signaling during repetitive stimulation with short (10-30 s) GnRH pulses and variable interpulse intervals in neonatal gonadotrophs perfused with Ca2+/Na+ -containing, Ca2+ -deficient/Na+ -containing, and Ca2+ -containing/Na+ -deficient media. In Ca2+/Na+ -containing medium, baseline Ca2+ oscillations recovered without refractory period and with a time constant of approximately 20 s, whereas the recovery of spike response occurred after 25-35 s refractory period and with a time constant of approximately 30 s. During repetitive GnRH stimulation, removal of Ca2+ had only a minor effect on baseline oscillations but abolished spike response, whereas removal of Na+ slightly extended duration of baseline oscillations and considerably prolonged spike response. These results indicate that two calcium handling mechanisms are operative in gonadotrophs: redistribution of calcium within InsP3-sensitive and -insensitive pools and a sodium-dependent calcium efflux followed by calcium influx. Redistribution of Ca2+ within the cell leads to rapid recovery of InsP3-dependent pool, whereas the Na+ -dependent Ca2+ efflux pathway is activated by spike response and limits the time of exposure to elevated cytosolic Ca2+ concentrations.
Zemkova
Hana
H
Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4. zemkova@biomed.cas.cz
Balik
Ales
A
Kretschmannova
Karla
K
Mazna
Petr
P
Stojilkovic
Stanko S
SS
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D007987:Gonadotropin-Releasing Hormone; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium