Role of integrative signaling through gap junctions in toxicology

Gap junctional intercellular communication (GJIC) plays a central role in coordinating signal-transduction pathways that control gene expression inside of cells with those of neighboring cells in maintaining the homeostasis of a tissue. The normal homeostatic set point of gap junctions within tissues is in an open state, and although transient closure of gap junctions in response to mitogenic effectors is normal, chronic closure of channels by continuous exposure to environmental and food-borne contaminants can result in adverse health effects such as cancer, teratogenesis, reproductive dysfunction, neuropathies, and cardiac arrhythmias. GJIC is the primary means of integrating signal transduction pathways controlling gene expression between contiguous cells. Thus, bioassay systems that can measure GJIC offer a central, more biosystems approach to assessing the potential for toxicants to epigenetically alter gene expression.