MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on September 5, 2007; DOI: 10.1124/mol.107.037150

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.107.037150v1
72/6/1576    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dai, X.-Q.
Right arrow Articles by Chen, X.-Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dai, X.-Q.
Right arrow Articles by Chen, X.-Z.


Received for publication April 17, 2007.
Revised September 4, 2007.
Accepted for publication September 4, 2007.

Inhibition of TRPP3 channel by amiloride and analogs

Xiao-Qing Dai 1, Alkarim Ramji 1, Yan Liu 1, Qiang Li 1, Edward Karpinski 1, Xing-Zhen Chen 1*

1 Membrane Protein Research Group, Department of Physiology, University of Alberta

* Address correspondence to: E-mail: xzchen{at}ualberta.ca

Abstract

TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca-activated channel permeable to Ca, Na and K. TRPP3 has been implicated in sour tasting in bipolar cells of tongue and in regulation of pH-sensitive action potential in spinal cord neurons. TRPP3 is also present in excitable and non-excitable cells of other tissues, including retina, brain, heart, testis and kidney, with unknown functions. Here we examined the functional modulation of TRPP3 channel by amiloride and its analogs, known to inhibit several ion channels and transporters and respond to all taste stimuli, using Xenopus oocytes expression, electrophysiology and radiotracer measurements. We found that amiloride and its analogs inhibit TRPP3 channel activities with different affinities. Radiolabelled 45Ca uptake showed that TRPP3-mediated Ca transport is inhibited by amiloride, phenamil, benzamil and EIPA. Two-microelectrode voltage clamp experiments revealed that TRPP3-mediated Ca-activated currents are substantially inhibited by amiloride analogs, in an order of potency of phenamil > benzamil > EIPA > amiloride, with the IC50 values of 0.14, 1.1, 10.5 and 143 µM, respectively. The inhibition potency positively correlated with the size of inhibitors. Using cell-attached patch clamping, we showed that the amiloride analogs decrease the open probability and mean open time, but have no effect on single-channel conductance. Study of inhibition by phenamil in the presence of previously reported inhibitor tetra-pentylammonium indicates that amiloride and organic cation inhibitors compete for binding the same site on TRPP3. TRPP3 may contribute to previously reported in vivo amiloride-sensitive cation transport.


Key words: Ion channel regulation, Calcium (Votage-Gated Channels), Single channel kinetics


This article has been cited by other articles:


Home page
 Am. J. Physiol. Renal Physiol.Home page
A. Cantone, X. Yang, Q. Yan, G. Giebisch, S. C. Hebert, and T. Wang
Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity
Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1366 - F1372.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics