title: Enhanced Ca(2+)-induced Ca(2+) release from intracellular stores contributes to catecholamine hypersecretion in adrenal chromaffin cells from spontaneously hypertensive rats.
abstract: Adrenal chromaffin cells (CCs) from spontaneously hypertensive rats (SHRs) secrete more catecholamine (CA) upon stimulation than CCs from normotensive Wistar Kyoto rats (WKY). Unitary CA exocytosis events, both spontaneous and stimulated, were amperometrically recorded from cultured WKY and SHR CCs. Both strains display spontaneous amperometric spikes but SHR CCs produce more spikes and of higher mean amplitude. After a brief stimulation with high K(+) or caffeine which produces voltage-gated Ca(2+) influx or intracellular Ca(2+) release, respectively, more spikes and of greater mean amplitude and unitary charge were recorded in SHR CCs. Consequently, peak cumulative charge was ~2-fold higher in SHR CCs. Ryanodine (10 μM), a specific blocker of the ryanodine receptors reduced depolarization-induced peak cumulative charge by ~10 % in WKY and ~77 % in SHR CCs, suggesting, a larger contribution of Ca(2+)-induced Ca(2+) release to CA exocytosis in SHR CCs. Accordingly, Ca(2+) imaging showed larger [Ca(2+)]i signals induced both by depolarization and caffeine in SHR CCs. Distribution amplitude histograms showed that small amperometric spikes (0-50 pA) are more frequent in WKY than in SHR CCs. Conversely, medium (50-190 pA) and large (190-290 pA) spikes are more numerous in SHR than in WKY CCs. This study reveals that the enhanced CA secretion in SHR CCs results from a combination of (1) larger depolarization-induced Ca(2+) transients, due to a greater Ca(2+)-induced intracellular Ca(2+) release, (2) more exocytosis events per time unit, and (3) a greater proportion of medium and large amperometric spikes probably due to a higher mean CA content per granule. Enhanced CA release by excessive amplification by Ca(2+) induced Ca(2+) release and larger granule catecholamine content contributes to the increased CA plasma levels and vasomotor tone in SHRs.
authors: Unidad de Investigación en Medicina Experimental, 5° piso Torre de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, Federal District, 04510, Mexico.|Hospital General de México, Mexico, Federal District, 06726, Mexico.
authors: Pedro
authors: P
authors: Segura-Chama
authors: Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, Federal District, 04510, Mexico.
authors: Patricia
authors: P
authors: López-Bistrain
authors: Unidad de Investigación en Medicina Experimental, 5° piso Torre de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, Federal District, 04510, Mexico.|Hospital General de México, Mexico, Federal District, 06726, Mexico.
authors: Elia Martha
authors: EM
authors: Pérez-Armendáriz
authors: Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, Federal District, 04510, Mexico.
authors: Nicolás
authors: N
authors: Jiménez-Pérez
authors: Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, Federal District, 04510, Mexico.
authors: Diana
authors: D
authors: Millán-Aldaco
authors: Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico, Federal District, 04510, Mexico. ahernan@ifc.unam.mx.
authors: Arturo
authors: A
authors: Hernández-Cruz
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects
chemical_list: D002395:Catecholamines; D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium
keywords: Amperometry; Calcium-induced calcium release; Catecholamine release; Chromaffin cell; Endoplasmic reticulum; Spontaneously hypertensive rat