“Independent regulation of electrical and chemical communication via Cx43 gap junctions”

ABSTRACT
Recently published data comparing permeability of Cx43 comprised gap junctions to either positively or negatively charged dyes and electrical conductance (permselectivity) across the same gap junction showed variability that exceeded two orders of magnitude in the relationship of these parameters. To ascertain whether this variable permselectivity is explained by variable charge or size selectivity of the comprising channels, the permeability of individual Cx43 gap junctions to dyes of differing size or charge was determined using dual dye injection techniques. The resulting data indicate that Cx43 junctions are size but not charge selective and do not show significant variability in either parameter. The absence of such variability suggests that the large range of junctional permselectivities previously reported is not due to an equivalently large range of individual channel selectivities. Rather, the data suggest that open Cx43 channels exist in one of two states, dye-permeable and dye-impermeable, both of which remain conductive to smaller ions. Regulation of the proportion of channels in each of these states would not alter junctional dye selectivity but would alter junctional permselectivity, which could represent a mechanism by which cells independently control electrical and chemical communication via Cx43 gap junctions. To investigate whether the C-terminus (CT) or phosphorylation of S368 therein influences dye selectivity we measured selectivity of junctions composed of Cx43-S368A or Cx43tr (terminus removed). Although the permselectivity of Cx43-S368A junctions is substantially reduced relative to wildtype, no change in dye selectivity (size or charge) was observed for either Cx43-S368A or Cx43tr. These data suggest that while the CT and phosphorylation of S368 therein may be involved in conversion of channels between dye permeable and impermeable states, neither significantly affects selectivity of dye permeable channels.