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F. Javier Alvarez-leefmans

MD, PhD
Department of PHARMACOLOGY & TOXICOLOGY
Wright State University
United States of America

F. Javier Alvarez-leefmans

Biography

Professor, Pharmacology & Toxicology , works in Medical Sciences Bldg 063, 3640 Colonel Glenn Hwy., Dayton, OH 45435-0001

Research Interest

Research Interests Research in his laboratory focuses on the molecular and cellular physiology of carrier protein molecules that actively transport chloride ions (Cl-) across the plasma membrane of neurons and epithelial cells. Specifically, they study some members of the cation-coupled-chloride contransporter gene/protein family SLC12A: the Na+, K+, 2 Cl- cotransporters (NKCC1 and NKCC2) and the K+-Cl- cotransporters (KCC1, 2, 3 and 4). These carrier proteins play key roles in: intracellular Cl- homeostasis in neurons, GABA- and glycine-mediated synaptic signaling, neuronal development, sensory transduction including nociception, transepithelial salt transport, cell water volume control, and extracellular K+ scavenging. Not surprisingly, altered function of these proteins underlies several pathologies and hence they have become significant targets for therapeutic interventions and translational research. To study the function of these proteins we use state-of-the-art live-cell imaging microscopy and fluorescent probes for measuring and manipulating intracellular ions and water in dissociated neurons and epithelial cells. Some of these optical methods have been developed in their lab, and are used in conjunction with molecular methods, knockout models, and several microanatomical techniques. Their current research involves two projects: Mechanisms regulating intracellular chloride in primary afferent neurons and their impact on GABA-mediated presynaptic inhibition and sensory transduction. This project aims at understanding the molecular mechanisms that determine intracellular Cl- concentration in primary afferent neurons, their regulation, and the role they play in presynaptic inhibition, acute somatic pain, neurogenic inflammation and proprioception. Roles of cation-coupled-chloride contransporters of choroid plexus epithelial cells in the regulation of cerebrospinal fluid ion composition. The choroid plexus epithelial cells (CPECs) form the blood-cerebrospinal fluid (CSF) barrier. CPECs secrete CSF and regulate its electrolyte composition. Regulation of CSF ion levels is fundamental for maintaining normal brain function. The overarching goal of this project is to understand how NKCC1, KCCs and aquaporins control the ion composition of the cerebrospinal fluid. Current emphasis is on the molecular and cellular mechanisms used by CPECs to regulate and maintain the CSF K+ concentration, a fundamental problem of broad physiological significance. CSF composition has a major impact on the fluid microenvironment of neurons and glial cells, and vice versa. Extracellular K+ homeostasis is critical for normal brain function; small changes in extracellular K+ profoundly affect neuronal excitability and osmotic water balance of glial cells and neurons

Publications

  • Alvarez-Leefmans FJ. and Delpire E. Physiology and Pathology of Chloride Transporters and Channels in the Nervous System. From molecules to diseases. Elsevier- Academic Press, San Diego, CA. 2009

  • Mao S, Garzon-Muvdi T, Di Fulvio M, Chen Y, Delpire E, Alvarez FJ, Alvarez-Leefmans, FJ. Molecular and functional expression of cation-chloride cotransporters in dorsal root ganglion neurons during postnatal maturation. Journal of Neurophysiology 108(3): 834-852 (2012)

  • Alvarez-Leefmans FJ. Intracellular Chloride Regulation. In: Cell Physiology Sourcebook (4th ed.), edited by Sperelakis N. London: Academic Press-Elsevier, p. 221-259. (2012).

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