title: Plasmalemmal sodium-calcium exchanger shapes the calcium and exocytotic signals of chromaffin cells at physiological temperature.
abstract: The activity of the plasmalemmal Na(+)/Ca(2+) exchanger (NCX) is highly sensitive to temperature. We took advantage of this fact to explore here the effects of the NCX blocker KB-R7943 (KBR) at 22 and 37°C on the kinetics of Ca(2+) currents (ICa), cytosolic Ca(2+) ([Ca(2+)]c) transients, and catecholamine release from bovine chromaffin cells (BCCs) stimulated with high K(+), caffeine, or histamine. At 22°C, the effects of KBR on those parameters were meager or nil. However, at 37°C whereby the NCX is moving Ca(2+) at a rate fivefold higher than at 22°C, various of the effects of KBR were pronounced, namely: 1) no effects on ICa; 2) reduction of the [Ca(2+)]c transient amplitude and slowing down of its rate of clearance; 3) blockade of the K(+)-elicited quantal release of catecholamine; 4) blockade of burst catecholamine release elicited by K(+); 5) no effect on catecholamine release elicited by short K(+) pulses (1-2 s) and blockade of the responses produced by longer K(+) pulses (3-5 s); and 6) potentiation of secretion elicited by histamine or caffeine. Furthermore, the more selective NCX blocker SEA0400 also potentiated the secretory responses to caffeine. The results suggest that at physiological temperature the NCX substantially contributes to shaping the kinetics of [Ca(2+)]c transients and the exocytotic responses elicited by Ca(2+) entry through Ca(2+) channels as well as by Ca(2+) release from the endoplasmic reticulum.
authors.affiliation: Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Juan-Fernando
authors.initials: JF
authors.lastname: Padín
authors.forename: José-Carlos
authors.initials: JC
authors.lastname: Fernández-Morales
authors.forename: Román
authors.initials: R
authors.lastname: Olivares
authors.forename: Stefan
authors.initials: S
authors.lastname: Vestring
authors.forename: Juan-Alberto
authors.initials: JA
authors.lastname: Arranz-Tagarro
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo-Gallardo
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Pascual
authors.forename: Luís
authors.initials: L
authors.lastname: Gandía
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
mesh_terms: D000818:Animals; D001965:Bromides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D017680:Potassium Compounds / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D013696:Temperature
chemical_list: D001965:Bromides; D002121:Calcium Channel Blockers; D002395:Catecholamines; D017680:Potassium Compounds; D011758:Pyrroles; D019831:Sodium-Calcium Exchanger; C071658:FPL 64176; D002110:Caffeine; D006632:Histamine; D009543:Nifedipine; C039004:potassium bromide; D011188:Potassium
keywords: KB-R7943; SEA0400; calcium signaling; chromaffin cells; exocytosis; sodium-calcium exchanger; temperature