• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.73-79
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• 2015

Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ) channels. Cx46 and Cx50 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 Cx46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, $1{\mu}M$) reversibly reduced outward hemichannel currents up to ~28% (n=4). However, overall shapes of Cx46 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 Cx46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.

• Journal of Life Science
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• v.17 no.11
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• pp.1517-1522
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• 2007

Gap junction channels formed by two adjacent cells allow the passage of small molecules up to ${\sim}\;1\;kDa$ between them. Hemichannel (connexon or half of gap junction) also behaves as a membrane channel like sodium or potassium channels in a single cell membrane. Among 26 types of connexin (Cx), $Cx32^*43E1$ (a chimera in which the first extracellular loop of Cx32 has been replaced with that of Cx43), Cx38, Cx46, and Cx50 form functional hemichannels as well as gap junction channels. Although it is known that Xenopus oocytes express endogenous connexin 38 (Cx38), its biophysical characteristics at single channel level are poorly understood. In this study, we performed single channel recordings from single Xenopus oocytes to acquire the biophysical properties of Cx38 including voltage-dependent gating and permeation (conductance and selectivity). The voltage-dependent fast and slow gatings of Cx38 hemichannel are distinct. Fast gating events occur at positive potentials and their open probabilities are low. In contrast, slow gatings dominate at negative potentials with high open probabilites. Based on hi-ionic experiments, Cx38 hemichannel is anion-selective. It will be interesting to test whether charged amino acid residues in the amino terminus of Cx38 are responsible for voltage gatings and permeation.