Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB).

Abstract

2-Aminoethoxydiphenyl borate (2-APB), an inositol 1,4,5-triphosphate receptor modulator, inhibits capacitive current transients measured in normal rat kidney and human embryonic kidney 293 cells, an indication of blocking gap junction channels between these cells. Here, we used the dual whole-cell patch-clamp method to study the actions of 2-APB on gap junction channels formed by selected connexins expressed in a communication-deficient neuroblastoma cell line (N2A). 2-APB dose-dependently and reversibly blocked junctional currents of connexin (Cx) 50 gap junction channels. The concentration-inhibition curve of 2-APB on the junctional current indicated an IC(50) of 3.7 microM, lower than that of most gap junction inhibitors. At a concentration of 20 microM, 2-APB also significantly blocked junctional conductance in cell pairs coupled by Cx26, Cx30, Cx36, Cx40, and Cx45 but did not appreciably affect coupling in cell pairs expressing Cx32, Cx43, and Cx46. Although concentration inhibition curves of 2-APB on Cx36 channels were similar to Cx50 (Cx36; IC(50), 3.0 microM), IC(50) values were higher for Cx43 (51.6 microM), Cx45 (18.1 microM), and Cx46 (29.4 microM). The blocking action of 2-APB did not substantially alter transjunctional voltage-dependent gating of Cx50 gap junction channels, and recordings from poorly coupled pairs of Cx50-transfected N2A cells indicated that 2-APB reduced gap junction channel open probability without changing the main state single-channel conductance. The differential efficacy of block by 2-APB of gap junction channels formed by different connexins may provide a useful tool that could be exploited in gap junction research to selectively block certain gap junction channel subtypes.

• Authors: Donglin Bai, Cristiane del Corsso, Miduturu Srinivas, David C Spray
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 319 Issue 3 Pg. 1452-8 (Dec 2006) ISSN: 0022-3565 [Print] United States
• PMID: 16985167 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Boron Compounds
• Connexins
• GJB2 protein, human
• Uncoupling Agents
• Connexin 26
• 2-aminoethoxydiphenyl borate

Topics

• Boron Compounds (pharmacology)
• Brain Neoplasms (metabolism)
• Cell Line, Tumor
• Connexin 26
• Connexins (drug effects, physiology)
• Dose-Response Relationship, Drug
• Gap Junctions (drug effects)
• Humans
• Ion Channel Gating (drug effects)
• Kinetics
• Neuroblastoma (metabolism)
• Patch-Clamp Techniques
• Uncoupling Agents (pharmacology)