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

Ke Tao Ma, Bing Cai Guan, Yu Qin Yang, Alfred Nuttall, Zhi-Gen Jiang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

2-Aminoethoxydiphenyl borate (2-APB) analogs are potentially better vascular gap junction blockers than others widely used, but they remain to be characterized. Using whole cell and intracellular recording techniques, we studied the actions of 2-APB and its potent analog diphenylborinic anhydride (DPBA) on vascular smooth muscle cells (VSMCs) and endothelial cells in situ of or dissociated from arteriolar segments of the cochlear spiral modiolar artery, brain artery, and mesenteric artery. We found that both 2-APB and DPBA reversibly suppressed the input conductance (Ginput) of in situ VSMCs (IC 50 ≈ 4-8 μM). Complete electrical isolation of the recorded VSMC was achieved at 100 μM. A similar gap junction blockade was observed in endothelial cell tubules of the spiral modiolar artery. Similar to the action of 18β-glycyrrhetinic acid (18β-GA), 2-APB and DPBA depolarized VSMCs. In dissociated VSMCs, 2-APB and DPBA inhibited the delayed rectifier K + current (IK) with an IC50 of ∼120 μM in the three vessels but with no significant effect on Ginput or the current-voltage relation between -140 and -40 mV. 2-APB inhibition of I K was more pronounced at potentials of ≤20 mV than at +40 mV and more marked on the fast component than on the slow component, which was mimicked by 4-aminopyridine but not by tetraethylammonium, nitrendipine, or charybdotoxin. In contrast, 18β-GA caused a linear inhibition of I K between 0 to +40 mV, which was similar to the action of tetraethylammonium or charybdotoxin. Finally, the 2-APB-induced inhibition of electrical coupling and IK was not affected by the inositol 1,4,5-trisphosphate receptor antagonist xestospongin C. We conclude that 2-APB analogs are a class of potent and reversible vascular gap junction blockers with a weak side effect of voltage-gated K+ channel inhibition. They 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number1
DOIs
StatePublished - Jan 2011

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Voltage-Gated Potassium Channels
Arterioles
Guinea Pigs
Vascular Smooth Muscle
Anhydrides
Gap Junctions
Smooth Muscle Myocytes
Glycyrrhetinic Acid
Charybdotoxin
Inositol 1,4,5-Trisphosphate Receptors
Tetraethylammonium
Arteries
Blood Vessels
Endothelial Cells
Nitrendipine
4-Aminopyridine
Mesenteric Arteries
2-aminoethoxydiphenyl borate
Cochlea
Patch-Clamp Techniques

Keywords

  • 18β-glycyrrhetinic acid
  • Cochlea
  • Diphenylborinic anhydride
  • Gap junction
  • Xestospongin C

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

2-Aminoethoxydiphenyl borate blocks electrical coupling and inhibits voltage-gated K+ channels in guinea pig arteriole cells. / Ma, Ke Tao; Guan, Bing Cai; Yang, Yu Qin; Nuttall, Alfred; Jiang, Zhi-Gen.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 300, No. 1, 01.2011.

Research output: Contribution to journalArticle

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AU - Jiang, Zhi-Gen

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N2 - 2-Aminoethoxydiphenyl borate (2-APB) analogs are potentially better vascular gap junction blockers than others widely used, but they remain to be characterized. Using whole cell and intracellular recording techniques, we studied the actions of 2-APB and its potent analog diphenylborinic anhydride (DPBA) on vascular smooth muscle cells (VSMCs) and endothelial cells in situ of or dissociated from arteriolar segments of the cochlear spiral modiolar artery, brain artery, and mesenteric artery. We found that both 2-APB and DPBA reversibly suppressed the input conductance (Ginput) of in situ VSMCs (IC 50 ≈ 4-8 μM). Complete electrical isolation of the recorded VSMC was achieved at 100 μM. A similar gap junction blockade was observed in endothelial cell tubules of the spiral modiolar artery. Similar to the action of 18β-glycyrrhetinic acid (18β-GA), 2-APB and DPBA depolarized VSMCs. In dissociated VSMCs, 2-APB and DPBA inhibited the delayed rectifier K + current (IK) with an IC50 of ∼120 μM in the three vessels but with no significant effect on Ginput or the current-voltage relation between -140 and -40 mV. 2-APB inhibition of I K was more pronounced at potentials of ≤20 mV than at +40 mV and more marked on the fast component than on the slow component, which was mimicked by 4-aminopyridine but not by tetraethylammonium, nitrendipine, or charybdotoxin. In contrast, 18β-GA caused a linear inhibition of I K between 0 to +40 mV, which was similar to the action of tetraethylammonium or charybdotoxin. Finally, the 2-APB-induced inhibition of electrical coupling and IK was not affected by the inositol 1,4,5-trisphosphate receptor antagonist xestospongin C. We conclude that 2-APB analogs are a class of potent and reversible vascular gap junction blockers with a weak side effect of voltage-gated K+ channel inhibition. They 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.

AB - 2-Aminoethoxydiphenyl borate (2-APB) analogs are potentially better vascular gap junction blockers than others widely used, but they remain to be characterized. Using whole cell and intracellular recording techniques, we studied the actions of 2-APB and its potent analog diphenylborinic anhydride (DPBA) on vascular smooth muscle cells (VSMCs) and endothelial cells in situ of or dissociated from arteriolar segments of the cochlear spiral modiolar artery, brain artery, and mesenteric artery. We found that both 2-APB and DPBA reversibly suppressed the input conductance (Ginput) of in situ VSMCs (IC 50 ≈ 4-8 μM). Complete electrical isolation of the recorded VSMC was achieved at 100 μM. A similar gap junction blockade was observed in endothelial cell tubules of the spiral modiolar artery. Similar to the action of 18β-glycyrrhetinic acid (18β-GA), 2-APB and DPBA depolarized VSMCs. In dissociated VSMCs, 2-APB and DPBA inhibited the delayed rectifier K + current (IK) with an IC50 of ∼120 μM in the three vessels but with no significant effect on Ginput or the current-voltage relation between -140 and -40 mV. 2-APB inhibition of I K was more pronounced at potentials of ≤20 mV than at +40 mV and more marked on the fast component than on the slow component, which was mimicked by 4-aminopyridine but not by tetraethylammonium, nitrendipine, or charybdotoxin. In contrast, 18β-GA caused a linear inhibition of I K between 0 to +40 mV, which was similar to the action of tetraethylammonium or charybdotoxin. Finally, the 2-APB-induced inhibition of electrical coupling and IK was not affected by the inositol 1,4,5-trisphosphate receptor antagonist xestospongin C. We conclude that 2-APB analogs are a class of potent and reversible vascular gap junction blockers with a weak side effect of voltage-gated K+ channel inhibition. They 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.

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