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Neurotensin modulates the amplitude and frequency of voltage‐activated Ca 2+ currents in frog pituitary melanotrophs: implication of the inositol triphosphate/protein kinase C pathway
Author(s) -
Belmeguenai Amor,
Leprince Jérôme,
To MarieChristine,
Vaudry Hubert,
Louiset Estelle
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02296.x
Subject(s) - protein kinase c , bapta , thapsigargin , calphostin , cyclopiazonic acid , medicine , endocrinology , biology , voltage dependent calcium channel , calphostin c , inositol , chemistry , biophysics , microbiology and biotechnology , intracellular , calcium , receptor , signal transduction , biochemistry
Many excitatory neurotransmitters and neuropeptides regulate the activity of neuronal and endocrine cells by modulating voltage‐operated Ca 2+ channels. Paradoxically, however, excitatory neuromediators that provoke mobilization of intracellular calcium from inositol trisphosphate (IP 3 )‐sensitive stores usually inhibit voltage‐gated Ca 2+ currents. We have recently demonstrated that neurotensin (NT) stimulates the electrical and secretory activities of frog pituitary melanotrophs, and increases intracellular calcium concentration in these cells. In the present study, we have investigated the effects of NT on Ca 2+ currents in cultured frog melanotrophs by using the perforated patch‐clamp technique. Frog neurotensin ( f NT) reduced the amplitude and facilitated the inactivation of both L‐ and N‐type Ca 2+ currents. Application of the membrane‐permeant Ca 2+ chelator BAPTA‐AM, the sarcoendoplasmic reticulum Ca 2+ ‐ATPase inhibitor thapsigargin, or the IP 3 receptor antagonist 2‐APB suppressed the reduction of Ca 2+ currents induced by f NT. Incubation of melanotrophs with the diacylglycerol analogue PMA, which causes desensitization of protein kinase C (PKC), or with the PKC inhibitors chelerythrine and calphostin C, reduced the inhibitory effect of f NT. The NT‐induced action potential waveforms, applied as voltage‐clamp commands, decreased the amplitude of Ca 2+ currents, and enhanced Ca 2+ influx by increasing the Ca 2+ spike frequency. Altogether, these data indicate that the inhibitory effect of f NT on Ca 2+ currents results from activation of the IP 3 /PKC pathway. The observation that NT controls Ca 2+ signalling through both amplitude and frequency modulations of Ca 2+ currents suggests that NT might induce spacial and temporal changes of intracellular Ca 2+ concentration leading to stimulation of exocytosis.