mice, studies revealed that cell coupling is essential for visual signaling. In the retina, ambient light levels influence cell coupling provided by gap junction channels, adapting the visual function for various lighting conditions. Cell coupling is governed by several mechanisms, including connexin expression. Decrock et al.. have discussed a multilevel platform via which connexins and pannexins can influence the following cellular functions within a tissue: (1) connexin gap junctional channels (GJCs) enable direct cell-cell communication of small molecules, (2) connexin hemichannels and pannexin channels can contribute to autocrine/paracrine signaling pathways, and (3) different structural domains of these proteins allow for channel-independent functions, such as cell-cell adhesion, interactions with the cytoskeleton, and the activation of intracellular signaling pathways. Thus, connexins and pannexins have multifaceted contributions to brain development and specific processes in the neuro-glio-vascular unit, including synaptic transmission and plasticity, glial signaling, vasomotor control, cell movement, and blood-brain barrier integrity in the mature CNS. Substrate specificity Different connexins may exhibit differing specificities for solutes. For example, adenosine passed about 12-fold better through channels formed by Cx32 while AMP and ADP passed about 8-fold better, and ATP greater than 300-fold better, through channels formed by Cx43. Thus, addition of phosphate to adenosine appears to shift its relative permeability from channels formed by Cx32 to channels formed by Cx43. This may have functional consequence because the energy status of a cell could be controlled via connexin expression and channel formation. Transport reaction The transport reaction catalyzed by connexin gap junctions is: Small molecules (cell 1 cytoplasm) ⇌ small molecules (cell 2 cytoplasm) Human connexins and clinical significance Gap junctions are essential for many physiological processes, such as the coordinated depolarization of cardiac muscle, proper embryonic development, and the conducted response in microvasculature. For this reason, deletion or mutation of the various connexin isoforms produces distinctive phenotypes and pathologies. While mutations in Cx43 are mostly linked to oculodentodigital dysplasia, Cx47 mutations are associated with Pelizaeus-Merzbacher-like disease and lymphedema. Cx40 mutations are principally linked to atrial fibrillation. Mutations in Cx37 have not yet been described, but polymorphisms in the Cx37 gene have been implicated in the development of arterial disease. References Sources External links Protein families Membrane proteins Transmembrane proteins Transmembrane transporters Transport proteins Integral membrane proteins