"c, Left, proportion of dual fluorescence-labelled cells for connexin pairs with known docking compatibility profiles. Right, FETCH scores for Cx43(F199L)-Cx43(F199L) and Cx26(K168V N176H)-Cx43 (ref. 26). Blue lines on the right-hand graph are the mean ± s.e.m. score for the known-negative distribution of connexin pairs with docking incompatibility. d, Schematic of M. americana Cx34.7 and Cx35 mutations in EL1 and EL2 used to screen for heterotypic-exclusive hemichannels."
Electrical synapses enable direct ion and small-molecule transfer between adjacent cells, coupling electrical activity across multiple organs including the brain. Gap junctions contain multiple channels, each formed by two docked hemichannels in the membranes of touching cells. Each hemichannel is an oligomer of six connexin monomers, with 21 connexin isoforms in humans. Many connexins form homotypic gap junctions by docking with the same isoform, while introducing heterologous connexins can create off-target electrical synapses between presynaptic neurons. A strategy uses exclusively heterotypic docking hemichannels to selectively modulate neural circuits. Fluorescence exchange and flow cytometry profiles assess docking compatibility, and dual-labeling proportions and FETCH scores quantify which connexin pairs dock effectively. Mutations in specific connexins are used to screen for heterotypic-exclusive hemichannels.
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