|
|
||||||||
1 Division of Biomedical Sciences, University of California, Riverside, California 92521; and 2 Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710
Na-K-2Cl cotransporter (NKCC)
and K-Cl cotransporter (KCC) play key roles in cell volume
regulation and epithelial Cl
transport. Reductions in
either cell volume or cytosolic Cl
concentration
([Cl
]i) stimulate a corrective uptake of
KCl and water via NKCC, whereas cell swelling triggers KCl loss via
KCC. The dependence of these transporters on volume and
[Cl
]i was evaluated in model duck red blood
cells. Replacement of [Cl
]i with
methanesulfonate elevated the volume set point at which NKCC activates
and KCC inactivates. The set point was insensitive to cytosolic ionic
strength. Reducing [Cl
]i at a constant
driving force for inward NKCC and outward KCC caused the cells to adopt
the new set point volume. Phosphopeptide maps of NKCC indicated that
activation by cell shrinkage or low [Cl
]i
is associated with phosphorylation of a similar constellation of
Ser/Thr sites. Like shrinkage, reduction of
[Cl
]i accelerated NKCC phosphorylation
after abrupt inhibition of the deactivating phosphatase with
calyculin A in vivo, whereas [Cl
] had no specific
effect on dephosphorylation in vitro. Our results indicate that NKCC
and KCC are reciprocally regulated by a negative feedback system dually
modulated by cell volume and [Cl
]. The major effect of
Cl
on NKCC is exerted through the volume-sensitive kinase
that phosphorylates the transport protein.
sodium-potassium-chloride cotransport; intracellular chloride; cell volume regulation; ionic strength; cell water content; sodium-potassium-chloride cotransporter phosphorylation
This article has been cited by other articles:
![]() |
H. I. Rocha-Gonzalez, S. Mao, and F. J. Alvarez-Leefmans Na+,K+,2Cl- Cotransport and Intracellular Chloride Regulation in Rat Primary Sensory Neurons: Thermodynamic and Kinetic Aspects J Neurophysiol, July 1, 2008; 100(1): 169 - 184. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. L. Jennings and J. Cui Chloride Homeostasis in Saccharomyces cerevisiae: High Affinity Influx, V-ATPase-dependent Sequestration, and Identification of a Candidate Cl- Sensor J. Gen. Physiol., March 31, 2008; 131(4): 379 - 391. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. K. Lauf, S. Misri, A. A. Chimote, and N. C. Adragna Apparent intermediate K conductance channel hyposmotic activation in human lens epithelial cells Am J Physiol Cell Physiol, March 1, 2008; 294(3): C820 - C832. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. K. Nielsen, A. K. Jensen, H. Harbak, S. C. Christensen, and L. O. Simonsen Cell content of phosphatidylinositol (4,5)bisphosphate in Ehrlich mouse ascites tumour cells in response to cell volume perturbations in anisotonic and in isosmotic media J. Physiol., August 1, 2007; 582(3): 1027 - 1036. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. T. Kahle, J. Rinehart, A. Ring, I. Gimenez, G. Gamba, S. C. Hebert, and R. P. Lifton WNK Protein Kinases Modulate Cellular Cl- Flux by Altering the Phosphorylation State of the Na-K-Cl and K-Cl Cotransporters. Physiology, October 1, 2006; 21: 326 - 335. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Strange, J. Denton, and K. Nehrke Ste20-Type Kinases: Evolutionarily Conserved Regulators of Ion Transport and Cell Volume Physiology, February 1, 2006; 21(1): 61 - 68. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. J Treharne, R. M Crawford, and A Mehta CFTR, chloride concentration and cell volume: could mammalian protein histidine phosphorylation play a latent role? Exp Physiol, January 1, 2006; 91(1): 131 - 139. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. D. Ciano-Oliveira, M. Lodyga, L. Fan, K. Szaszi, H. Hosoya, O. D. Rotstein, and A. Kapus Is myosin light-chain phosphorylation a regulatory signal for the osmotic activation of the Na+-K+-2Cl- cotransporter? Am J Physiol Cell Physiol, July 1, 2005; 289(1): C68 - C81. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Kreindler, A. D. Jackson, P. A. Kemp, R. J. Bridges, and H. Danahay Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L894 - L902. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Denton, K. Nehrke, X. Yin, R. Morrison, and K. Strange GCK-3, a Newly Identified Ste20 Kinase, Binds To and Regulates the Activity of a Cell Cycle-dependent ClC Anion Channel J. Gen. Physiol., January 31, 2005; 125(2): 113 - 125. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. R. Williams and J. A. Payne Cation transport by the neuronal K+-Cl- cotransporter KCC2: thermodynamics and kinetics of alternate transport modes Am J Physiol Cell Physiol, October 1, 2004; 287(4): C919 - C931. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. F. X. Dowd and B. Forbush PASK (Proline-Alanine-rich STE20-related Kinase), a Regulatory Kinase of the Na-K-Cl Cotransporter (NKCC1) J. Biol. Chem., July 18, 2003; 278(30): 27347 - 27353. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |