Gap junction channels are composed of proteins in the connexin family. There are almost two dozen mammalian connexins. "Cx" followed by a number, for example, Cx43, denotes each connexin. The number predicts molecular mass, although this prediction may not always be accurate. A gap junction channel consists of two hexameric hemichannels, one in each cell. For some connexins, e.g., Cx32, hemichannels are formed in the endoplasmic reticulum (ER), while for others, such as Cx43 and Cx46, the hemichannels are assembled in the Golgi apparatus . Regulated trafficking of connexin hemichannels to the plasma membrane enables modulation of channel number at the intercellular interface.
The major vascular connexins are Cx37, Cx40, and Cx43, which are expressed differing extents depending on tissue type and location . These connexins, when expressed by the same cell, have been shown to form heteromeric (mixed) gap junction channels including Cx40 : Cx43, Cx37 : Cx43, and Cx37 : Cx40 channels.
The ability of connexins to intermix defines permeability and gating characteristics of the gap junction channel. Connexins also have multiple conductance states. The interpretation of cell-cell coupling by gap junctions requires consideration of both the extent of compatibility between connexin subtypes and the physical-chemical properties of the probe being used. A good approach is to obtain electrophysiological quantifications of net ionic flux across gap junctions simultaneously with those of fluorescent dye transfer. This dual approach normalizes channel permeability against channel surface area. Using this approach, Burt et al. found that communication through heteromeric Cx40 : Cx43 channels increased with an increase in the amount of Cx43 relative to Cx40 . Other examples of heteromeric gap junction channels with unique permeability characteristics include the following connexin pairings: Cx37:Cx43, Cx40 : Cx43, and Cx43 : Cx45. Given that different classes of vascular cells express different ratios of these connexins, this suggests that intercellular communication is regulated through differential connexin expression.
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