Integration of cytoplasmic calcium and membrane potential oscillations maintains calcium signaling in pituitary gonadotrophs.
Pituitary gonadotrophs exhibit spontaneous low-amplitude fluctuations in cytoplasmic calcium concentration ([Ca2+]i) due to intermittent firing of nifedipine-sensitive action potentials. The hypothalamic neuropeptide, gonadotropin-releasing hormone, terminates such spontaneous [Ca2+]i transients and plasma-membrane electrical activity and initiates high-amplitude [Ca2+]i oscillations and concomitant oscillations in membrane potential (Vm). The onset of agonist-induced [Ca2+]i oscillations is not dependent on Vm or extracellular Ca2+ but is associated with plasma-membrane hyperpolarization interrupted by regular waves of depolarization with firing of action potentials at the peak of each wave. The Vm and Ca2+ oscillations are interdependent during continued gonadotropin-releasing hormone action (greater than 3-5 min), when sustained Ca2+ entry is necessary for the maintenance of [Ca2+]i spiking. The initial and sustained agonist-induced Ca2+ transients and Vm oscillations are abolished by blockade of endoplasmic reticulum Ca(2+)-ATPase, consistent with the role of Ca2+ re-uptake by internal stores in the oscillatory response during both phases. Such a pattern of synchronization of electrical activity and Ca2+ spiking in cells regulated by Ca(2+)-mobilizing receptors shows that the operation of the cytoplasmic oscillator can be integrated with a plasma-membrane oscillator to provide a long-lasting signal during sustained agonist stimulation.
Stojilković
S S
SS
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Kukuljan
M
M
Iida
T
T
Rojas
E
E
Catt
K J
KJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000502:physiology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009543:Nifedipine / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology; D010052:Ovariectomy; D010507:Periodicity; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction
D009761:Nystatin; D007987:Gonadotropin-Releasing Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium