Calcium entry, calcium redistribution, and exocytosis.
At a given cytosolic domain of a chromaffin cell, the rate and amplitude of the Ca(2+) concentration, [Ca(2+)](c), depend on at least three efficient regulatory mechanisms: (1) the plasmalemmal Ca(2+) channels; (2) the endoplasmic reticulum (ER); and (3) the mitochondria. High-voltage activated Ca(2+) channels of the L, N, P/Q, and R subtypes are expressed with different densities in various mammalian species; they are regulated by G proteins coupled to purinergic and opiate receptors, as well as by voltage and the local changes of [Ca(2+)](c). Targeted aequorin and confocal microscopy show that Ca(2+) entry through Ca(2+) channels can refill the ER to near millimolar concentrations and causes the release of ER Ca(2+) (CICR). We have also seen that, depending on its degree of filling, the ER may act as a sink or source of Ca(2+) that modulates the release of catecholamine. Targeted aequorins with different Ca(2+) affinities show that mitochondria undergo surprisingly rapid millimolar Ca(2+) transients ([Ca(2+)](M)) upon stimulation of chromaffin cells with ACh, high K(+), or caffeine. Physiological stimuli generate [Ca(2+)](c) microdomains at these functional complexes in which the local subplasmalemmal [Ca(2+)](c) rises abruptly from 0.1 micro M to about 50 micro M. This triggers CICR, mitochondrial Ca(2+) uptake, and exocytosis in nearby secretory active sites. That this is true is shown by the observation that protonophores abolish mitochondrial Ca(2+) uptake and drastically increase catecholamine release by 3- to 5-fold. This increase is likely due to acceleration of vesicle transport from a reserve pool to a ready-release vesicle pool; such transport might be controlled by Ca(2+) redistribution to the cytoskeleton, through CICR and/or mitochondrial Ca(2+) release.
Cuchillo-Ibanez
Inmaculada
I
Instituto Teófilo Hernando, Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Albillos
Almudena
A
Aldea
Marcos
M
Arroyo
Gloria
G
Fuentealba
Jorge
J
Garcia
Antonio G
AG
D000818:Animals; D001665:Binding Sites; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000378:metabolism*; D003599:Cytoskeleton; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary
D002395:Catecholamines; D002110:Caffeine; D011188:Potassium; D002118:Calcium