2‐Aminoethoxydiphenyl borate (2‐APB) suppression on gap junction coupling is associated with a weak inhibition of voltage‐gated K + ‐channels in guinea‐pig arteriolar cells

2‐APB was reported to inhibit the conductance of gap junctions (GP) composed of Cx26 and/or Cx32 and electro‐coupling‐mediated EDHF and relaxation in an artery. Using whole‐cell and intracellular recording techniques, we studied the 2‐APB potency in blocking vascular GP and the side actions on non‐GP channels in vascular smooth muscle cells (VSMC) and endothelial cells (EC) of cochlear spiral modiolar artery (SMA) and arterioles from the brain and mesentery. Results showed that 1) 2‐APB and its analog DPBA both concentration‐dependently suppressed the input conductance (G input ) of a VSMC in situ of a vessel segment with an IC 50 of 4–8 μM. A complete electrical isolation of the VSMC was achieved at 100 μM. A similar GP blockade exhibited in tubules of ECs. 2) 2‐APB and DPBA depolarized the cells more strongly than 18β‐glycyrrhetinic acid (18βGA). 3) On dispersed VSMCs, 2‐APB and DPBA had no significant effect on G input or I/V relation between −140 and −40 mV but inhibited the delayed rectifying potassium current (K DR ) with a similar IC 50 of ~120 μM for both analogs, compared to ~50 μM for 18βGA. 5) The inhibition of K DR was always more pronounced at potentials ≤20 mV than at 40 mV and more pronounced for the fast than the slow component in step‐activated current, which was mimicked and nullified by 4‐AP but not TEA. 6) The junctional and non‐junctional actions were not affected by IP 3 receptor antagonist xestospongin C. We conclude that 2‐APB and DPBA are about half as potent as 18βGA in blocking the arteriolar GP and K DR channels. The K DR inhibition of 2‐APB is mainly on voltage‐gated, not Ca 2+ ‐activated, K + ‐channels. Supported by NIH NIDCD DC 004716 (ZGJ)