NAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cells

NAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cells

Author Pereira, Gustavo J. S. Autor UNIFESP Google Scholar
Hirata, Hanako Autor UNIFESP Google Scholar
Garcez-do-Carmo, Lucia Autor UNIFESP Google Scholar
Stilhano, Roberta S. Autor UNIFESP Google Scholar
Ureshino, Rodrigo P. Autor UNIFESP Google Scholar
Medaglia, Natalia C. Autor UNIFESP Google Scholar
Han, Sang W. Autor UNIFESP Google Scholar
Churchill, Grant Google Scholar
Bincoletto, Claudia Autor UNIFESP Google Scholar
Patel, Sandip Google Scholar
Smaili, Soraya Soubhi Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Univ Oxford
Abstract Nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as an important modulator of Ca2+ release from the endo-lysosomal system in a variety of cells by a new and ubiquitous class of endo-lysosomal ion channels known as the two-pore channels (TPCs). However, the role of TPCs in NAADP action in smooth muscle is not known. in the present work, we investigated the effects of NAADP in gastric smooth muscle cells and its ability to release Ca2+ by TPCs. We show that Ca2+ signals mediated by NAADP were inhibited by disrupting Ca2+ handling by either acidic organelles (using bafilomycin A1) or the Endoplasmic Reticulum (using thapsigargin, ryanodine or 2-APB). Transcripts for endogenous TPC1 and TPC2 were readily detected and recombinant TPCs localized to the endosomes and/or lysosomes. Overexpression of wild-type TPCs but not pore mutants enhanced NAADP-mediated cytosolic Ca2+ signals. Desensitizing the NAADP pathway inhibited Ca2+-responses to extracellular stimulation with carbachol but not ATP. Taken together, these results indicate that NAADP likely induces Ca2+ release from the endolysosomal system through TPCs which is subsequently amplified via the ER in an agonist-specific manner. Thus, we suggest a second messenger role for NAADP in smooth muscle cells. (C) 2014 Elsevier B.V. All rights reserved.
Keywords NAADP
Gastric smooth muscle cells
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Biotechnology and Biological Sciences Research Council
Grant number FAPESP: 2008/11.515-3
CNPq: 482030/2010-0
CAPES: BB/G013721/1
Date 2014-08-01
Published in Cell Calcium. Edinburgh: Churchill Livingstone, v. 56, n. 2, p. 51-58, 2014.
ISSN 0143-4160 (Sherpa/Romeo, impact factor)
Publisher Churchill Livingstone
Extent 51-58
Access rights Closed access
Type Article
Web of Science ID WOS:000340323600002

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