Block of Specific Gap Junction Channel Subtypes by 2-Aminoethoxydiphenyl Borate (2-APB)

  title={Block of Specific Gap Junction Channel Subtypes by 2-Aminoethoxydiphenyl Borate (2-APB)},
  author={Donglin Bai and C del Corsso and Miduturu Srinivas and David C. Spray},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={1452 - 1458}
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… 

Figures and Tables from this paper

The effects of 2-aminoethoxydiphenyl borate and diphenylboronic anhydride on gap junctions composed of Connexin43 in TM₄ sertoli cells.

2-APB and DPBA inhibit GJ communication through decreasing Cx43 expression in TM₄ cells, indicating that decreased GJ coupling resumes after the two compounds are washed out.

2-Aminoethoxydiphenyl borate blocks electrical coupling and inhibits voltage-gated K+ channels in guinea pig arteriole cells.

2-APB analogs could be gap junction blockers superior to 18β-GA only when Ca(2+)-actived K(+) channel inhibition by the latter is a concern but inositol 1,4,5-trisphosphate receptor and voltage-gated K(+ channel inhibitions are not.

2-Aminoethyl diphenyl borinate (2-APB) inhibits TRPM7 channels through an intracellular acidification mechanism

It is found that in Jurkat T lymphocytes, 100–300 µM extracellular 2-APB reversibly inhibits TRPM7 channels when internal HEPES concentration is low (1 mM), and that increasing the concentration to 140 mM abolishes the 2- APB effect.

Screening of gap junction antagonists on dye coupling in the rabbit retina

The combination of potency, water solubility and reversibility, and the effects on dye coupling were easily reversible suggest that MFA may be a useful compound to manipulate gap junction coupling.

Carbenoxolone inhibits volume-regulated anion conductance in cultured rat cortical astroglia

Findings support the notion that CBX could affect astroglial ability to modulate neuronal activity by suppressing excitatory amino acid release through VRAC, and provide a possible mechanistic clue for the neuroprotective effect of CBX in vivo.

Functional roles of the amino terminal domain in determining biophysical properties of Cx50 gap junction channels

These data are consistent with a structural model where the NT domain of Cx50 lines the gap junction pore and plays an important role in sensing Vj and in the subsequent conformational changes leading to gating, as well as in limiting the rate of ion permeation.

Molecular Modeling Suggests Homologous 2-APB Binding Sites in Connexins 26 and 32

Virtual screening results imply molecules with similar activity on Cx26 and Cx32 as 2- APB can be found, and modeling suggests that 2-APB binds to similar sites inside the pores of Cx 26 and CX32.

Human Connexin Channel Specificity of Classical and New Gap Junction Inhibitors

This study presents the specificity of published inhibitors toward several connexin isoforms expressed in the brain and identifies seven new inhibitors, with high functional reversibility and different relative selectivity toward isoforms, which might provide new insights in understanding numerous pathophysiological processes involving gap junctions.

Transfection of mammalian cells with connexins and measurement of voltage sensitivity of their gap junctions

General protocols presented here are currently used to transfect mammalian cells with connexins and to study the biophysical properties of the heterologously expressed connexin channels and for analysis of voltage dependence and single-channel conductance of gap junction channels.



Closure of gap junction channels by arylaminobenzoates.

It is proposed that FFA inhibits gap junctions by inducing a conformational change in the protein upon binding to a site that is presumably located within the membrane.

Besides affecting intracellular calcium signaling, 2‐APB reversibly blocks gap junctional coupling in confluent monolayers, thereby allowing the measurement of single‐cell membrane currents in undissociated cells

It is shown in monolayers of normal rat kidney cells (NRK/49F) that 2‐APB completely and reversibly blocks gap junctional intercellular communication at concentrations similar to that required for inhibition of PGF2α‐induced increases in intracellular calcium.

Block of TRPC5 channels by 2‐aminoethoxydiphenyl borate: a differential, extracellular and voltage‐dependent effect

The data indicate a specific and functionally important binding site on TRPC5 that enables block by 2‐APB and the site is only available via an extracellular route and the block shows mild voltage‐dependence.

Quinine blocks specific gap junction channel subtypes

Quinine offers a potentially useful method to block certain types of gap junction channels, including those between neurons that are formed by Cx36, and quinine derivatives that are excluded from other types of membrane channels may provide molecules with connexin-specific as well as con Nexin-selective blocking activity.

2-aminoethoxydiphenyl borane activates a novel calcium-permeable cation channel.

The influence of 2-APB on capacitative calcium entry and intracellular Ca2+ concentrations in rat basophilic leukemia (RBL-2H3 m1) cells is examined and the presence of a novel, ligand-gated calcium-permeable channel is revealed.

Voltage dependence of macroscopic and unitary currents of gap junction channels formed by mouse connexin50 expressed in rat neuroblastoma cells

Investigation of the macroscopic and single channel gating characteristics of connexin (Cx) 50 gap junction channels between pairs of N2A neuroblastoma cells transfected with mouse Cx50 DNA revealed a lower permeability to anions than to cations, which has important implications for understanding the role ofconnexins in tissues where CX50 is a major gap junction component.

Fenamates: a novel class of reversible gap junction blockers.

Inhibition of gap junctional communication by fenamates did not involve changes in intracellular calcium or pH, and was unrelated to protein kinase C activity or an inhibition of cyclooxygenase activity.

Regulation of Connexin Channels by pH

The identification of taurine as a cytoplasmic compound that directly interacts with and modulates connexin channel activity is likely to facilitate understanding of cellular modulation of con Nexin channels and lead to the development of reagents for use in structure-function studies of connexIn protein.

Connexin32 gap junction channels in stably transfected cells: unitary conductance.