Gap junctions are essential for many physiological processes including cardiac and smooth muscle contraction, regulation of neuronal excitability and epithelial electrolyte transport [3-5]. Gap junction channels allow the passive diffusion of molecules of up to 1,000 Daltons which can include nutrients, metabolites and second messengers (such as IP₃) as well as cations and anions. 21 connexin genes and 3 pannexin genes which are structurally related to the invertebrate innexin genes) code for gap junction proteins in humans. Each connexin gap junction comprises 2 hemichannels or 'connexons' which are themselves formed from 6 connexin molecules. The various connexins have been observed to combine into both homomeric and heteromeric combinations, each of which may exhibit different functional properties. It is also suggested that individual hemichannels formed by a number of different connexins might be functional in at least some cells [6]. Connexins have a common topology, with four α-helical transmembrane domains, two extracellular loops, a cytoplasmic loop, and N- and C-termini located on the cytoplasmic membrane face. In mice, the most abundant connexins in electrical synapses in the brain seem to be Cx36, Cx45 and Cx57 [9]. Mutations in connexin genes are associated with the occurrence of a number of pathologies, such as peripheral neuropathies, cardiovascular diseases and hereditary deafness. The pannexin genes Px1 and Px2 are widely expressed in the mammalian brain [10]. Like the connexins, at least some of the pannexins can form hemichannels [3,7].

Connexins are most commonly named according to their molecular weights, so, for example, Cx23 is the connexin protein of 23 kDa. This can cause confusion when comparing between species – for example, the mouse connexin Cx57 is orthologous to the human connexin Cx62. No natural toxin or specific inhibitor of junctional channels has been identified yet however two compounds often used experimentally to block connexins are carbenoxolone and flufenamic acid [8]. At least some pannexin hemichannels are more sensitive to carbenoxolone than connexins but much less sensitive to flufenamic acid [2]. It has been suggested that 2-aminoethoxydiphenyl borate (2-APB) may be a more effective blocker of some connexin channel subtypes (Cx26, Cx30, Cx36, Cx40, Cx45, Cx50) compared to others (Cx32, Cx43, Cx46, [1]).

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