Gap Junction Voltage Dependence

All vertebrate gap junction channels display voltage-dependent gating. Historically, voltage-dependent behaviors have been characterized as being transjunctional voltage (Vj) and membrane voltage (Vm) dependent. The transjunctional voltage dependence of gap junction channels composed of two identical hemichan-nels, each composed of identical connexins subunits (a homotypic channel) is usually symmetric and is often referred as Vj-dependent gating. Vj steps of equal amplitude but opposite polarity will result in junctional currents that are mirror images of each other in terms of magnitude and kinetics (Harris et al., 1981; Spray et al., 1981). Figure 1 in Oh et al. (2000) illustrates such symmetric (slow) Vj dependence, as well as the characteristic steady state " residual " junctional conductance. It is interesting to note that the first demonstration of voltage dependence in cell-to-cell communication is best considered to be a subset of Vj dependence. It is the rectifying or asymmetric voltage dependence first observed in the crayfish rectifying synapse by Fursphan and Potter (1959), where the kinetics are quite rapid, which gave rise to the term fast Vj dependence. Similar rapid asymmetric effects of voltage on junctional con-ductance have been described in vertebrate gap junctions as well. It is usually observed in heterotypic gap junction channels. Heterotypic channels are composed of two hemichannels of different connexin composition. The hemichannel of one cell can be composed of Cx32, for example, while the adjacent cell contributes a hemichannel composed of Cx26. Many such combinations of connexins produce rectifying or asymmetric Vj dependence. This fast Vj dependence is thought to be embodied in the rectification of single channel con-ductance (Bukauskas et al., 1995). That is, single channel conductance of heterotypic gap junction channels is dependent on Vj and its polarity. Gap junction channels composed of hemichannels that contain more than one type of connexin are called heteromeric forms and display a variety of behaviors intermediate between those of homotypic and heterotypic forms (He et al., 1999; Brink et al., 1997). At the single-channel level, two types of gating that can account for the behavior of macroscopic junctional conductance are typically observed. At the single-channel level, the term Vj gating refers to rapid transitions between a fully open state and a subconductance state. A second form of gating in hemichannels has been provisionally termed loop gating and is characterized by a series of step-like transitions between the open and closed states with a time course of many milliseconds …