期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 44, 页码 17542-17547出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0701254104
关键词
transient receptor potential; canonical; Ca2+ entry; acinar cells; muscarinic receptor
资金
- Intramural NIH HHS Funding Source: Medline
- NCRR NIH HHS [P20 RR017699-077011, P20 RR017699] Funding Source: Medline
- NIDCR NIH HHS [R01 DE017102-01A1, DE017102, R01 DE017102-03, R01 DE017102, R01 DE017102-02] Funding Source: Medline
- Wellcome Trust [060988] Funding Source: Medline
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 Ca2+-dependent potassium channel activity, which depends on Ca2+ 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.
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