Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Abolished InsP3R2 function inhibits sweat secretion in both humans and mice
Joakim Klar, … , Katsuhiko Mikoshiba, Niklas Dahl
Joakim Klar, … , Katsuhiko Mikoshiba, Niklas Dahl
Published October 20, 2014
Citation Information: J Clin Invest. 2014;124(11):4773-4780. https://doi.org/10.1172/JCI70720.
View: Text | PDF
Research Article Genetics Article has an altmetric score of 76

Abolished InsP3R2 function inhibits sweat secretion in both humans and mice

  • Text
  • PDF
Abstract

There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2), that was present in all affected family members. We determined that the mutation is localized within the pore forming region of InsP3R2 and abrogates Ca2+ release from the endoplasmic reticulum, which suggests that intracellular Ca2+ release by InsP3R2 in clear cells of the sweat glands is important for eccrine sweat production. Itpr2–/– mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2–/– animals revealed a decrease in Ca2+ response compared with controls. Together, our data indicate that loss of InsP3R2-mediated Ca2+ release causes isolated anhidrosis in humans and suggest that specific InsP3R inhibitors have the potential to reduce sweat production in hyperhidrosis.

Authors

Joakim Klar, Chihiro Hisatsune, Shahid M. Baig, Muhammad Tariq, Anna C.V. Johansson, Mahmood Rasool, Naveed Altaf Malik, Adam Ameur, Kotomi Sugiura, Lars Feuk, Katsuhiko Mikoshiba, Niklas Dahl

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2009 Total
Citations: 4 2 3 5 7 5 3 3 6 7 2 1 1 49
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2016 (7)

Title and authors Publication Year
Store-operated Ca2+ entry regulates Ca2+-activated chloride channels and eccrine sweat gland function
Axel Concepcion, Martin Vaeth, Larry Wagner, Miriam Eckstein, Lee Hecht, Jun Yang, David Crottes, Maximilian Seidl, Hyosup Shin, Carl Weidinger, Scott Cameron, Stuart E. Turvey, Thomas B. Issekutz, isabelle Meyts, Rodrigo Lacruz, Mario Ćuk, David Yule, Stefan Feske
Journal of Clinical Investigation 2016
Ca 2+ transport and signalling in enamel cells: Calcium in enamel cells
MK Nurbaeva, M Eckstein, S Feske, RS Lacruz
The Journal of Physiology 2016
Cardiac inositol 1,4,5-trisphosphate receptors
MI Garcia, D Boehning
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2016
Regulation of epithelial ion transport in exocrine glands by store-operated Ca2+ entry
AR Concepcion, S Feske
Cell Calcium 2016
Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca2+ release
KJ Alzayady, L Wang, R Chandrasekhar, LE Wagner, FV Petegem, DI Yule
Science signaling 2016
Genetic ablation of IP 3 receptor 2 increases cytokines and decreases survival of SOD1 G93A mice
KA Staats, S Humblet-Baron, A Bento-Abreu, W Scheveneels, A Nikolaou, K Deckers, R Lemmens, A Goris, JA van Ginderachter, PV Damme, C Hisatsune, K Mikoshiba, A Liston, W Robberecht, LV Bosch
Human Molecular Genetics 2016
K + channel mechanisms underlying cholinergic cutaneous vasodilation and sweating in young humans: roles of K Ca , K ATP , and K V channels?
N Fujii, JC Louie, BD McNeely, SY Zhang, MA Tran, GP Kenny
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology 2016

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 5 news outlets
Blogged by 3
Posted by 23 X users
Mentioned by 1 weibo users
On 1 Facebook pages
Reddited by 1
68 readers on Mendeley
See more details