Bisphenol A and 4-tert-octylphenol inhibit C×46 hemichannel currents

Abstract

Connexins (C×) are membrane proteins and monomers for forming gap junction (GJ) channels. C×46 and C×50 are also known to function as conductive hemichannels. As part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors were used to examine their effect on C×46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of C×46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of C×46 hemichannels up to ∼18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, 1 μM) reversibly reduced outward hemichannel currents up to ∼28% (n=4). However, overall shapes of C×46 hemichannel current traces (outward and inward currents) were not changed by these drugs. These results suggest that BPA and OP are likely to occupy the pore of C×46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.