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Am J Physiol Cell Physiol 292: C106-C114, 2007. First published July 12, 2006; doi:10.1152/ajpcell.00209.2006
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TRANSLATIONAL PHYSIOLOGY

EGF and HB-EGF modulate inward potassium current in human bladder urothelial cells from normal and interstitial cystitis patients

Yan Sun,1 Mingkui Chen,3 Benjamin H. Lowentritt,1 P. Sean Van Zijl,1 Kristopher R. Koch,2 Susan Keay,2 J. Marc Simard,3 and Toby C. Chai1

1Department of Surgery, Division of Urology, 2Department of Medicine, Division of Infectious Diseases, and 3Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland

Submitted 26 April 2006 ; accepted in final form 5 July 2006

ABSTRACT

Interstitial cystitis (IC) is an idiopathic condition characterized by bladder hyperalgesia. Studies have shown cytokine and purinergic signaling abnormalities in cultured bladder urothelial cells (BUC) from IC patients. We performed single-cell electrophysiological studies in both normal and IC BUC. A strongly inward rectifying potassium current with conductance of the Kir2.1 channel was identified in normal BUC. This current was significantly reduced in IC BUC. Kir2.1 protein and mRNA were detected in both IC and normal BUC. Epidermal growth factor (EGF) caused a dose-dependent decrease in the inward potassium current in normal BUC. EGF is secreted in higher amounts by IC BUC and is known to decrease Kir2.1 conductance by phosphorylation of Kir2.1. Genistein, a nonspecific phosphorylation inhibitor, increased the inward potassium current in IC BUC and blocked the effect of EGF on normal BUC. Treatment of IC BUC with heparin-binding epidermal growth factor-like growth factor (HB-EGF), previously shown to be secreted in lower amounts by IC BUC, significantly increased inward potassium current. These data show that the inward potassium current in BUC can be modulated by EGF and HB-EGF. Changes in BUC membrane potassium conductance caused by altered levels of EGF and HB-EGF may therefore play a role in the pathophysiology of IC.

epidermal growth factor; heparin-binding epidermal growth factor-like growth factor


Address for reprint requests and other correspondence: T. C. Chai, Univ. of Maryland, Division of Urology, 22 S. Greene St., S8D18, Baltimore, MD 21201 (e-mail: tchai{at}smail.umaryland.edu)




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