Function of the voltage gate of gap junction channels: selective exclusion of molecules

Gap junction channels span the membranes of two adjacent cells and allow the gated transit of molecules as large as second messengers from cell to cell. In vertebrates, gap junctions are composed of proteins from the connexin (cx) gene family. Gap junction channels formed by most connexins are affected by transjunctional voltage. The function of the voltage gate is unclear, because substantial electrical coupling typically remains with activated gates because of the channels dwelling in subconductance rather than closed states. Here, we find in Xenopus oocytes expressing cx43 or cx46 that the activated voltage gate preferentially restricts the passage of larger ions, such as fluorescent tracer molecules and cAMP, while having little effect on the electrical coupling arising from the passage of small electrolytes. Thus, a conceivable physiological role of the voltage gate is to selectively restrict the passage of large molecules between cells while allowing electrical coupling.