Gap junction delta-2 protein (Connexin 36) (Cx36)

Gap junction delta-2 protein, commonly known as Connexin 36 (Cx36), is a transmembrane protein that forms hexameric hemichannels (connexons) which dock with adjacent cells to create gap junction channels (UniProt P60570). These channels facilitate the direct exchange of ions and small metabolites, playing a vital role in electrical coupling and neuronal synchronization within the central nervous system (PubMed: 15173207). Cx36 is predominantly expressed in inhibitory interneurons and retinal neurons, as well as in pancreatic beta cells where it coordinates insulin secretion (PubMed: 21489144). In disease states, altered Cx36 expression or function is linked to epilepsy, schizophrenia, and impaired glucose tolerance. Pharmacological agents such as quinine and mefloquine act as blockers of Cx36 channels, and research into more selective modulators is ongoing for the treatment of seizures and metabolic disorders (PubMed: 11739557). The protein is also essential for the normal function of the rod-mediated visual pathway in the retina. Because Cx36 is the primary connexin forming electrical synapses in the brain, it is a key target for modulating network oscillations. However, the high degree of homology between connexin isoforms makes the development of specific drugs challenging.

Other names

Connexin 36GJD2Gap junction alpha-9GJA9Cx36Gap junction protein delta 2

Direct blockade or modulation of the pore-forming connexin subunits to inhibit or enhance the passage of ions and small molecules between coupled cells.