GnRH-induced cytosolic calcium oscillations in pituitary gonadotrophs: phase resetting by membrane depolarization.
Cultured rat pituitary gonadotrophs under whole-cell voltage clamp conditions respond to the hypothalamic hormone GnRH with synchronized oscillatory changes in both cytosolic Ca2+ concentration ([Ca2+]i) and [Ca2+]i-activated, apamin-sensitive K+ current (IK(Ca)). We found, and report here for the first time, that in GnRH-stimulated cells a brief depolarizing pulse can elicit a transient [Ca2+]i rise similar to the endogenous cycle. Furthermore, Ca2+ entry during a single depolarizing pulse was found to shift the phase of subsequent endogenous [Ca2+]i oscillations, which thereafter continue to occur at their previous frequency before the pulse. Application of two consecutive depolarizing pulses showed that the size of the [Ca2+]i rise evoked by the second pulse depended on the time lapsed between two consecutive pulses, indicating that each endogenous or evoked [Ca2+]i rise cycle leaves the Ca2+ release mechanism of the gonadotroph in a refractory state. Recovery from this condition can be described by an exponential function of the time lapsed between the pulses (time constant of ca. 1 s). We propose that the underlying mechanism in both refractoriness after endogenous cycles and phase resetting by a brief pulse of Ca2+ entry involves the InsP3 receptor-channel molecule presumed to be located on the cytosolic aspect of the endoplasmic reticulum membrane.
Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health Bethesda, Maryland 20892, USA.
L A
LA
Vergara
S S
SS
Stojilkovic
E
E
Rojas
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007031:Hypothalamus / Q000502:physiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009991:Oscillometry; D010052:Ovariectomy; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D015221:Potassium Channels; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium