What Do We Know about Selective Permeability of Connexin Channels among Second Messengers?
The first evidence for a direct intercellular pathway permeable to molecules came in the 1920s from studies of dye spread in cardiac cells (Schmidtmann, 1925). Many studies, beginning in the mid-1960s, later demonstrated the permeation of exogenous tracers of various kinds through gap junction channels. Evidence that gap junctions could mediate intercellular movement of endogenous metabolites (then called “metabolic cooperation”) soon followed (Subak-Sharpe et al., 1966; Gilula et al., 1972), as did the seminal demonstrations of movement of cAMP through junctional channels (Tsien and Weingart, 1974; Lawrence et al., 1978). Since these initial findings, gap junction channels have been shown to be permeable to a wide variety of cytoplasmic molecules, including inositol phosphates, nucleotide triphosphates, cyclic monophosphates, nucleotides, amino acids, glutathione, calcium ion, glucose and its metabolites, cytosolic pH buffers, small RNAs, and small peptides (for review see Harris, 200
