Charge at the 46th residue of connexin 50 is crucial for the gap-junctional unitary conductance and transjunctional voltage-dependent gating

摘要

Key points Gap-junction (GJ) channels provide direct intercellular communication and are twice the length of most membrane channels, yet they often have high efficiency in permeation of ions, which is reflected by large unitary channel conductance ((j)). To reveal the key factors in determining the (j) of a lens GJ channel, we studied connexin 50 mutant GJ channels, where a negatively or positively charged residue was introduced into a pore-lining domain. The results indicate that the pore surface electrostatic potential is a dictating factor for the connexin 50 GJ channel (j). A change in the local resistance of the channel pore associated with these mutant channels is an important factor for their voltage-dependent gating properties. The combination of dual patch clamp and homology structure modelling is a powerful approach in revealing molecular mechanisms of GJ gating and ion permeation.