Secretion from rat neurohypophysial nerve terminals (neurosecretosomes) rapidly inactivates despite continued elevation of intracellular Ca2+.
Cytoplasmic calcium concentration was measured in neurosecretory nerve terminals (neurosecretosomes) isolated from rat neurohypophyses by fura-2 fluorescence measurements and digital video microscopy. Hormone release and cytoplasmic calcium concentration were measured during depolarizations induced by elevated extracellular potassium concentration. During prolonged depolarizations with 55 mM [K+]o, the cytoplasmic calcium concentration remained elevated as long as depolarization persisted, while secretion inactivated after the initial sharp rise. The amplitude and duration of the increase in [Ca2+]i was dependent on the degree of depolarization such that upon low levels of depolarizations (12.5 mM or 25 mM [K+]o), the calcium responses were smaller and relatively transient, and with higher levels of depolarization (55 mM [K+]o) the responses were sustained and were higher in amplitude. Responses to low levels of depolarization were less sensitive to the dihydropyridine calcium channel blocker, nimodipine, while the increase in [Ca2+]i induced by 55 mM [K+]o became transient, and was significantly smaller. These observations suggest that these peptidergic nerve terminals possess at least two different types of voltage-gated calcium channels. Removal of extracellular sodium resulted in a significant increase in [Ca2+]i and secretion in the absence of depolarizing stimulus, suggesting that sodium-calcium exchange mechanism is operative in these nerve terminals. Although the [Ca2+]i increase was of similar magnitude to the depolarization-induced changes, the resultant secretion was 10-fold lower, but the rate of inactivation of secretion, however, was comparable.
Fatatis
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Section on Neuronal Secretory Systems, NICHD, National Institutes of Health, Bethesda, MD 20892.
Holtzclaw
L
L
Payza
K
K
Russell
J T
JT
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002138:Calibration; D003600:Cytosol / Q000378:metabolism*; D016257:Fura-2; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D010909:Pituitary Hormones, Posterior / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014741:Video Recording
D010909:Pituitary Hormones, Posterior; D009553:Nimodipine; D002118:Calcium; D016257:Fura-2