Connexin43 and connexin50 channels exhibit different permeability to the second messenger inositol triphosphate

Gap junction channels made of different connexins have distinct permeability to second messengers, which could affect many cell processes, including lens epithelial cell division. Here, we have compared the permeability of IP₃ and Ca²⁺ through channels made from two connexins, Cx43 and Cx50, that are highly expressed in vertebrate lens epithelial cells. Solute transfer was measured while simultaneously monitoring junctional conductance via dual whole-cell/perforated patch clamp. HeLa cells expressing Cx43 or Cx50 were loaded with Fluo-8, and IP₃ or Ca²⁺ were delivered via patch pipette to one cell of a pair, or to a monolayer while fluorescence intensity changes were recorded. Cx43 channels were permeable to IP₃ and Ca²⁺. Conversely, Cx50 channels were impermeable to IP₃, while exhibiting high permeation of Ca²⁺. Reduced Cx50 permeability to IP₃ could play a role in regulating cell division and homeostasis in the lens.