Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice

Xibao Liu, Kwong Tai Cheng, Bidhan C. Bandyopadhyay, Biswaranjan Pani, Alexander Dietrich, Biman C. Paria, William D. Swaim, David Beech, Eda Yildrim, Brij B. Singh, Lutz Birnbaumer, Indu S. Ambudkar

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

Agonist-induced Ca2+ entry via store-operated Ca2+ (SOC) channels is suggested to regulate a wide variety of cellular functions, including salivary gland fluid secretion. However, the molecular components of these channels and their physiological function(s) are largely unknown. Here we report that attenuation of SOC current underlies salivary gland dysfunction in mice lacking transient receptor potential 1 (TRPC1). Neurotransmitter-regulated salivary gland fluid secretion in TRPC1-deficient TRPC1(-/-) mice was severely decreased (by 70%). Further, agonist- and thapsigargin-stimulated SOC channel activity was significantly reduced in salivary gland acinar cells isolated from TRPC1(-/-) mice. Deletion of TRPC1 also eliminated sustained Ca 2+-dependent potassium channel activity, which depends on Ca 2+ entry and is required for fluid secretion. Expression of key proteins involved in fluid secretion and Ca2+ signaling, including STIM1 and other TRPC channels, was not altered. Together, these data demonstrate that reduced SOC entry accounts for the severe loss of salivary gland fluid secretion in TRPC1(-/-) mice. Thus, TRPC1 is a critical component of the SOC channel in salivary gland acinar cells and is essential for neurotransmitter- regulation of fluid secretion.

Original languageEnglish (US)
Pages (from-to)17542-17547
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number44
DOIs
StatePublished - Oct 30 2007

Keywords

  • Acinar cells
  • Ca entry
  • Canonical
  • Muscarinic receptor
  • Transient receptor potential

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Attenuation of store-operated Ca<sup>2+</sup> current impairs salivary gland fluid secretion in TRPC1(-/-) mice'. Together they form a unique fingerprint.

Cite this