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Current Research:
The retinal pigment epithelium (RPE) is a transporting cell layer that
plays a critical role in vision. It helps control the composition and
volume of the extracellular space surrounding the photoreceptor outer
segments, which is necessary for retinal adhesion and normal
photoreceptor function. Ion channels are important components of the
transport pathways that carry out solute and fluid transport across the
RPE. Dr. Hughes is performing research that will identify the
biophysical properties of potassium, chloride and sodium channels so
that we can better understand how they function in coordination with
ion pumps and co-transporters. Using the patch-clamp technique to
measure whole-cell currents in acutely dissociated RPE cells from
bovine and human retina, his research group is characterizing ion
conductances in terms of ion selectivity, voltage dependence, kinetics
of activation and deactivation, and blocker sensitivity. This
information provides a "fingerprint" that enables Dr. Hughes and his research team to extend these investigations to single channels and intact tissues.
In a related project, Dr. Hughes is pursuing the genetic code for inwardly rectifying potassium channels in the RPE and neural retina using molecular cloning techniques. Elucidation of the genetic code for these channels may provide more insight into their protein structure and regulation as well as their possible role in retinal disease.
Representative
Publications:
Yang D, Pan A, Swaminathan A, Kumar G, Hughes BA. Expression and localization of the inwardly rectifying K+ channel Kir7.1 in native bovine retinal pigment epithelium. IOVS 2003;44:3178-3185.
Yang D, Ernst SA, MacCallum DA, Hughes BA. Expression of the inwardly rectifying K+ channel Kir2.1 in native bovine corneal endothelial cells. IOVS 2003;44:3511-3519.
Yuan Y, Shimura M, Hughes BA. Regulation of inwardly rectifying K+ channels in retinal pigment epithelial cells by intracellular pH. J Physiol (Lond) 2003;549:429-438.
Shimura M, Yuan Y, Chang JT, Zhang S, Campochiaro PA, Zack DJ, Hughes BA. Expression and permeation properties of the K+ channel Kir7.1 in the retinal pigment epithelium. J Physiology 2001;531:329-346.
Hughes BA, Kumar GA, Swaminathan A, Yan D, Yuan Y, Sharma A, Plumley L, Yang-Feng TL, Swaroop A. Cloning and functional expression of human retinal Kir2.4, a pH-sensitive, inwardly rectifying K+ channel. Amer J Physiol Cell 2000;279: C771-C784.
Hughes BA, Takahira M. ATP-dependent regulation of the inwardly rectifying K current in bovine retinal pigment epithelial cells. Amer J Physiol 1998;275;C1372-C1383.
Takahira M, Hughes BA. Isolated bovine retinal pigment epithelial cells express delayed rectifier- and M-type potassium currents. Amer J Physiol 1997;273:C1-C14.
Hughes BA, Takahira M. Inwardly rectifying K+ currents in isolated human retinal pigment epithelial cells. IOVS 1996;37:1125-1139.
Hughes BA, Takahira M, Segawa Y. An outwardly rectifying K+ current active near resting potential in human retinal pigment epithelial cells. Amer J Physiol 1995;269:C179-187.
Hughes BA, Shaikh A, Ahmad A. Effects of Ba2+ and Cs+ on apical membrane K+ conductance in toad retinal pigment epithelium. Amer J Physiol 1995;268:C1164-1172.
Segawa Y, Hughes BA. Properties of the inwardly rectifying K+ conductance in the toad retinal pigment epithelium. J Physiol (Lond) 1994;476:41-53.
Hughes BA, Segawa Y. cAMP-activated chloride currents in amphibian retinal pigment epithelial cells. J Physiol (Lond) 1993;466:746-76.
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