Modulation of plasma membrane calcium-ATPase activity by local calcium microdomains near CRAC channels in human T cells.
AuthorsBautista DM, Lewis RS
JournalJ Physiol
PubMed ID14966303
'The spatial distribution of Ca(2+) signalling molecules is critical for establishing specific interactions that control Ca(2+) signal generation and transduction. In many cells, close physical coupling of Ca(2+) channels and their targets enables precise and robust activation of effector molecules through local [Ca(2+)](i) elevation in microdomains. In T cells, the ... More
Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+.
AuthorsSørensen JB, Fernández-Chacón R, Südhof TC, Neher E
JournalJ Gen Physiol
PubMed ID12939392
'We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2+ sensor for fast neurosecretion by analyzing the intracellular Ca2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated synaptotagmin C2A domain. The mutation (R233Q) causes a twofold increase in the KD of Ca2+-dependent phospholipid binding ... More
Hyperinsulinism induced by targeted suppression of beta cell KATP channels.
'ATP-sensitive K+ (K(ATP)) channels couple cell metabolism to electrical activity. To probe the role of K(ATP) in glucose-induced insulin secretion, we have generated transgenic mice expressing a dominant-negative, GFP-tagged K(ATP) channel subunit in which residues 132-134 (Gly-Tyr-Gly) in the selectivity filter were replaced by Ala-Ala-Ala, under control of the insulin ... More
Rab3A negatively regulates activity-dependent modulation of exocytosis in bovine adrenal chromaffin cells.
AuthorsThiagarajan R, Tewolde T, Li Y, Becker PL, Rich MM, Engisch KL
JournalJ Physiol
PubMed ID14694148
'Members of the Rab family of monomeric GTPases have been implicated in vesicle trafficking, and Rab3A, located on synaptic vesicles in neurones and secretory vesicles in neuroendocrine cells, is likely to be involved in vesicle fusion leading to neurotransmitter release. A hydrolysis-deficient mutant of Rab3A, Rab3AQ81L, has been shown to ... More
Abnormal intracellular calcium homeostasis in sympathetic neurons from young prehypertensive rats.
AuthorsLi D, Lee CW, Buckler K, Parekh A, Herring N, Paterson DJ,
JournalHypertension
PubMed ID22252398
'Hypertension is associated with cardiac noradrenergic hyperactivity, although it is not clear whether this precedes or follows the development of hypertension itself. We hypothesized that Ca(2+) homeostasis in postganglionic sympathetic neurons is impaired in spontaneously hypertensive rats (SHRs) and may occur before the development of hypertension. The depolarization-induced rise in ... More
Amphiphilic, tri-block copolymers provide potent membrane-targeted neuroprotection.
AuthorsMarks JD, Pan CY, Bushell T, Cromie W, Lee RC
JournalFASEB J
PubMed ID11292683
New ratiometric fluorescent calcium indicators with moderately attenuated binding affinities.
AuthorsGee KR, Archer EA, Lapham LA, Leonard ME, Zhou ZL, Bingham J, Diwu Z
JournalBioorg Med Chem Lett
PubMed ID10915039
Mono-halogenated derivatives of the calcium indicators fura-2 and indo-1 were synthesized and their spectroscopic properties evaluated. Halogenation ortho or para to the bridging oxygen in the BAPTA nucleus had a more pronounced weakening effect on binding affinity than in the meta position in the fura derivatives. Two new excitation ratioable ... More
RyR2 and calpain-10 delineate a novel apoptosis pathway in pancreatic islets.
AuthorsJohnson JD, Han Z, Otani K, Ye H, Zhang Y, Wu H, Horikawa Y, Misler S, Bell GI, Polonsky KS
JournalJ Biol Chem
PubMed ID15044459
Cells are programmed to die when critical signaling and metabolic pathways are disrupted. Inhibiting the type 2 ryanodine receptor (RyR2) in human and mouse pancreatic beta-cells markedly increased apoptosis. This mode of programmed cell death was not associated with robust caspase-3 activation prompting a search for an alternative mechanism. Increased ... More
Calcium influx through receptor-operated channel induces mitochondria-triggered paraptotic cell death.
AuthorsJambrina E, Alonso R, Alcalde M, del Carmen Rodríguez M, Serrano A, Martínez-A C, García-Sancho J, Izquierdo M
JournalJ Biol Chem
PubMed ID12571238
We address the specific role of cytoplasmic Ca(2+) overload as a cell death trigger by expressing a receptor-operated specific Ca(2+) channel, vanilloid receptor subtype 1 (VR1), in Jurkat cells. Ca(2+) uptake through the VR1 channel, but not capacitative Ca(2+) influx stimulated by the muscarinic type 1 receptor, induced sustained intracellular ... More
Mitochondrial Ca(2+)-induced Ca(2+) release mediated by the Ca(2+) uniporter.
AuthorsMontero M, Alonso MT, Albillos A, García-Sancho J, Alvarez J
JournalMol Biol Cell
PubMed ID11160823
We have reported that a population of chromaffin cell mitochondria takes up large amounts of Ca(2+) during cell stimulation. The present study focuses on the pathways for mitochondrial Ca(2+) efflux. Treatment with protonophores before cell stimulation abolished mitochondrial Ca(2+) uptake and increased the cytosolic [Ca(2+)] ([Ca(2+)](c)) peak induced by the ... More
Redistribution of Ca2+ among cytosol and organella during stimulation of bovine chromaffin cells.
AuthorsVillalobos C, Nuñez L, Montero M, García AG, Alonso MT, Chamero P, Alvarez J, García-Sancho J
JournalFASEB J
PubMed ID11874983
Recent results indicate that Ca2+ transport by organella contributes to shaping Ca2+ signals and exocytosis in adrenal chromaffin cells. Therefore, accurate measurements of [Ca2+] inside cytoplasmic organella are essential for a comprehensive analysis of the Ca2+ redistribution that follows cell stimulation. Here we have studied changes in Ca2+ inside the ... More
Polycarboxylate fluorescent indicators as ion concentration probes in biological systems.
AuthorsKaterinopoulos HE, Foukaraki E
JournalCurr Med Chem
PubMed ID11860359
A large number of techniques have been applied to monitor the function of free metal ions in biological systems. Fluorescent ion probes have evolved into an extremely useful tool for contemporary experimentalists. Polycarboxylate indicators are widely used in the determination of metal ion concentrations, especially due to their cell membrane ... More
Characterization of a range of fura dyes with two-photon excitation.
AuthorsWokosin DL, Loughrey CM, Smith GL
JournalBiophys J
PubMed ID14990500
Two-photon excitation (TPE) spectra of Fura-2, -4F, -6F, -FF, and Furaptra were characterized using a tunable (750-850 nM) ultra-short pulse laser. Two-photon fluorescence of these dyes was studied in free solution and in the cytosol of isolated rabbit ventricular cardiomyocytes. The TPE spectra of the Ca(2+)-free and Ca(2+)-bound forms of ... More
Nicotinic acid-adenine dinucleotide phosphate-sensitive calcium stores initiate insulin signaling in human beta cells.
AuthorsJohnson JD, Misler S
JournalProc Natl Acad Sci U S A
PubMed ID12381785
Recent studies suggest a role for autocrine insulin signaling in beta cells, but the mechanism and function of insulin-stimulated Ca(2+) signals is uncharacterized. We examined Ca(2+)-dependent insulin signaling in human beta cells. Two hundred nanomolar insulin elevated [Ca(2+)](c) to 284 +/- 27 nM above baseline in approximately 30% of Fura-4F-loaded ... More