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, its novel neuronal KC 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 alternation in the activity of cotransporters? In the life of a neuron intracellular [Cl^-] undergoes synamic changes, such as will lead to alterations in GABAergic 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.

Representative Publications

Gillen, C.M., S. Brill, J.A. Payne, and B. Forbush III. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human: a new member of the cation-chloride cotransporter family. J. Biol. Chem. 271 (27): 16237-16244, 1996.

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, 1996.

Payne, J.A. Functional characterization of the neuronal-specific K-Cl cotransporter: implications for [K⁺] regulation. Am. J. Physiol. Cell Physiol. 273: C1516-C1525, 1997.

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, 1999.

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.

Gulyas, A.I., A. Sik, J.A. Payne, K. Kaila, and T.F. Freund. The K-Cl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in the rat hippocampus. Eur. J. Neurosci. 13: 2205-2217, 2001.

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.

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 downregulation of the neuron-specific K-Cl cotransporter, KCC2. J. Neurosci. 24:4683-4691, 2004.

Williams, J.R. 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. 287: C919-C931, 2004.

Vanden Heuvel, G.B., J.A. Payne, P. Igarashi, and B. Forbush III. Expression of the basolateral Na-K-Cl cotransporter during mouse nephrogenesis and embryonic development. Gene Expr. Patterns 6(8): 1000-1006, 2006.

Lee, H.H.C., J.A. Walker, J.R. Williams, R.J. Goodier, J.A. Payne, and S.J. Moss. Direct PKC-dependent phosphorylation regulates the cell surface stability, endocytosis, and activity of the potassium chloride cotransporter, KCC2. J. Biol. Chem., 282(41): 29777-29784, 2007.

Chung, C.-Y. and J.A. Payne. Modulaton of GABAergic signaling: role of neuronal chloride. In Encyclopedia of Basic Epilepsy Research, (Ed. P.A. Schwartzkroin). Elsevier, 2009.

Payne, J.A. The potassium-chloride cotransporters: from cloning to structure and function. In Physiology and Pathology of Chloride Transporters and Channels in the Nervous System: From Molecules to Diseases. (Ed. F.J. Alvarez-Leefmans and E. Delpire). Elsevier, in press

Recent/Current Teaching

HPH400, Human Physiology, Co-Instructor of Record
HPH493C, Special Studies Module
MCP210B, Advanced Physiology