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RESEARCH INTERESTS
My laboratory examines the cellular physiology of the cation chloride cotransport proteins, including the Na-K-Cl cotransporter (NKCC) and K-Cl cotransporter (KCC). We are particularly interested in the function of these transport proteins in excitable cells, neurons and muscle cells. We have identified a neuron-specific isoform of the K-Cl cotransporter (KCC2) that is important in maintaining low intracellular [Cl-] for the proper function of ligand-gated anion channels (GABAA and glycine receptors) in postsynaptic inhibition of mature neurons. Moreover, this novel neuronal KCC may have an important role in the regulation of external [K+] in the brain. The regulation of the cation chloride cotransporters is an important area of our research. Both NKCC and KCC2 appear to have significant roles in regulating intracellular [Cl-] and cell volume of neurons. How are changes in these cell parameters linked to alteration in the activity of the cotransporters? In the life of a neuron intracellular [Cl-] undergoes dynamic changes, such as during neuronal development or following tramatic insults. These changes in intracellular [Cl-] will lead to alterations in GABAAergic transmission. Are changes NKCC and KCC2 transport activity linked to these events and if so how? We are studying the regulation of NKCC and KCC2 by examining changes in both their kinetic activity and surface protein expression. In addition to their function at the cell level, I am interested in the structure of these proteins and how they function at the molecular level. How do the cotransporters interact with the ions they transport and the inhibitors they bind? Where are these sites of interaction within the protein? How do the cotransporters interact with other regulatory proteins? My laboratory uses whole animal, cellular, and molecular experimentation to answer many of these questions.
SELECTED PUBLICATIONS
| 2006 |
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Vanden Heuvel, G.B. J.A. Payne, P. Igarashi, and B. Forbush III. Expression of the basolateral Na-K-Cl cotransporter during mouse neprogenesis and embryonic development. Gene Expr. Patterns 6(8): 1000-1006, 2006. |
| 2004 |
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Bartho, P., T. Freund, J.A. Payne, nd L. Acsady. Differential distribution of the K-Cl cotransporter KCC2 in the thalamic relay and reticular nuclei. Eur. J. Neuroscie. 20(4): 965-975, 2004. |
| 2004 |
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Williams, J.R. and J.A. Payne. Cation transport by the neuronal K-Cl cotransporter, KC2: Thermodynamics and kinetics of alternate transport modes. Am. J. Physiol. Cell Physiol. 287: C919-C931, 2004. |
| 2004 |
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Rivera, C., J. Voipio, J. Thomas-Crusells, H. Li, Z. Emri, S. Sipila, J.A. Payne, L. Minichiello, M. Saarma, and K. Kaila. Mechanism of activity-dependent down-regulation of KCC2. J. Neurosci. 24(19): 4683-4691. |
| 2003 |
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Payne, J.A., C. Rivera, J. Voipio, and K. Kaila. Cation chloride cotransporters and their role in neuronal communication, development, and trauma. Trends in Neurosci., 26(4): 199-206, 2003. |
| 2001 |
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Payne, J.A., C. Ferrell, and C.-Y. Chung. Endogenous and exogenous Na-K-Cl cotransporter expression in a low K+-resistant mutant MDCK cell line. Am. J. Physiol. Cell Physiol. 280: C1607-C1615. |
| 2001 |
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Gulyas, A.I., A. Sik, J.A. Payne, K. Kaila, and T.F. Freund. High expression of the K-Cl cotransporter, KCC2, in postsynaptic membranes associated with excitatory inputs of the rat hippocampus emphasizes a dual role in ion and water homeostasis. Eur. J. Neurosci. 13: 2205-2217. |
| 2000 |
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Vu, T.Q., J.A. Payne, and D.R. Copenhagen. Localization and developmental expression patterns of the neuronal K-Cl cotransporter (KCC2) in the rat retina. J. Neurosci. 20(4): 1414-1423. |
| 2000 |
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Vardi, N., L.-L. Zhang, J.A. Payne, and P. Sterling. Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA. J. Neurosci. 20(20): 7657-7663. |
| 1999 |
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Williams, J.R., J.W. Sharp, V.G. Kumari, M. Wilson, and J.A. Payne. The neuron-specific K-Cl cotransporter, KCC2: antibody development and initial characterization of the protein. J. Biol. Chem. 274(18): 12656-12664. |
| 1999 |
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Rivera, C., J. Voipio, J.A. Payne, E. Ruusuvuori, H. Lahtinen, K. Lamsa, U. Pirvola, M. Saarma, K. Kaila. The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397: 251-255. |
| 1997 |
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Payne, J.A. Functional characterization of the neuronal-specific K-Cl cotransporter: implications for [K+]o regulation. Am. J. Physiol. Cell Physiol. 273: C1516-C1525. |
| 1996 |
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Payne, J.A., T.J. Stevenson, and L. Donaldson. Molecular characterization of a putative K-Cl cotransporter in rat brain: a neuronal-specific isoform. J. Biol. Chem. 271 (27): 16245-16252. |
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