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

Producción científica: Articlerevisión exhaustiva

191 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)17542-17547
Número de páginas6
PublicaciónProceedings of the National Academy of Sciences of the United States of America
Volumen104
N.º44
DOI
EstadoPublished - oct 30 2007
Publicado de forma externa

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