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J Biol Chem, Vol. 274, Issue 35, 25121-25129, August 27, 1999
ATP-dependent Activation of KCa and
ROMK-type KATP Channels in Human Submandibular Gland
Ductal Cells
Xibao
Liu,
Brij B.
Singh, and
Indu S.
Ambudkar
From the Secretory Physiology Section, Gene Therapy and
Therapeutics Branch, NIDCR, National Institutes of Health,
Bethesda, Maryland 20892
[Ca2+]i and membrane
current were measured in human submandibular gland ductal (HSG) cells
to determine the regulation of salivary cell function by ATP. 1-10
µM ATP activated internal Ca2+ release,
outward Ca2+-dependent K+ channel
(KCa), and inward store-operated Ca2+ current
(ISOC). The subsequent addition of 100 µM ATP activated an inwardly rectifying K+
current, without increasing [Ca2+]i. The
K+ current was also stimulated by ATP in cells treated with
thapsigargin in a Ca2+-free medium and was blocked by
glibenclamide and tolbutamide, but not by charybdotoxin. This suggests
the involvement of a Ca2+-independent,
sulfonylurea-sensitive K+ channel (KATP). UTP
mimicked the low [ATP] effects, while benzoyl-ATP activated internal
Ca2+ release, a Ca2+ influx pathway, and
KCa. Thus, ATP acts via P2U (P2Y2)
and P2Z (P2X7) receptors to increase
[Ca2+]i and activate KCa, but not
KATP. Importantly, (i) ROMK1 and the cystic fibrosis
transmembrane regulator protein (but not SUR1, SUR2A, or SUR2B) and
(ii) cAMP-stimulated Cl and K+ currents were
detected in HSG cells. These data demonstrate for the first time that a
ROMK-type KATP channel is present in salivary gland duct
cells that is regulated by extracellular ATP and possibly by the cystic
fibrosis transmembrane regulator. This reveals a potentially novel
mechanism for K+ secretion in these cells.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.
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