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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