Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice.
Agonist-induced Ca(2+) entry via store-operated Ca(2+) (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 Ca(2+) 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.
Liu
Xibao
X
Secretory Physiology Section, Gene Therapy and Therapeutic Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Cheng
Kwong Tai
KT
Bandyopadhyay
Bidhan C
BC
Pani
Biswaranjan
B
Dietrich
Alexander
A
Paria
Biman C
BC
Swaim
William D
WD
Beech
David
D
Yildrim
Eda
E
Singh
Brij B
BB
Birnbaumer
Lutz
L
Ambudkar
Indu S
IS
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D015221:Potassium Channels / Q000378:metabolism; D012463:Saliva / Q000378:metabolism*; D012469:Salivary Glands / Q000378:metabolism*; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D015221:Potassium Channels; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D002118:Calcium