ABSTRACT

The activity of gap junction channels is modulated acutely by several classes of agents including ions, specifically protons and calcium, the products and enzymes released or activated by second messenger cascades, and a variety of lipophilic agents, including some alkanols, volatile anesthetics, and fatty acids. Once concentrated at the channel-lipid interface, closure of the gap junction channel likely reflects the ability of many of the compounds to perturb membrane lipid and protein structure rather than interaction with a specific amino acid residue of the channel protein. The activity of the cardiac gap junction channel is influenced by several second messenger systems, and this class of agents may be the regulators used by the heart to modulate junctional conductance in response to physiological stimuli. A number of seemingly unrelated lipophilic substances reduce reversibly the conductance of cardiac gap junctions, including short-chain alkanols such as heptanol and octanol, volatile anesthetics such as halothane, and a variety of fatty acids.