Cardiac gap junction conductance is highly regulated by various physiological and pharmacological factors, primarily through the open-closed gating of individual channels.
Cardiac Gap Junction Channel Regulation. Synchronization of pacemaker activity and cardiac action potential propagation is dependent upon the maintenance of electrical communication via gap junctions. Gap junction channels in mammalian heart are formed by a 43‐kilodalton (kD) protein, connexin43, and have a unitary conductance of 50 picosiemens (pS). In embryonic chick heart, three gap junction proteins of 42, 43, and 45 kD have been cloned, the functional properties of which have not been individually identified. Unitary channel conductances ranging from 40‐240 pS have been reported, but conductances of 40‐80 and 160 pS are most frequently observed in embryonic chick heart. Developmental changes in transjunctional voltage dependence are known to occur and may be correlated with differential expression of the three chick connexins during development. Gap junction conductance (g j ) is highly regulated, being maintained or increased by ATP and cAMP‐dependent pathways. Conversely, g j is reduced by treatment with various lipophilic agents (e.g., n‐alkanols, arachidonic acid, halothane), large transjunctional potentials, increasing intracellular cation (e.g., H + , Ca 2+ ) concentrations, and tyrosine phophorylation of rat connexin43. It is unclear at this time if any of the regulatory mechanisms can mediate beat‐to‐beat fluctuations in g j of normal myocardium. Most available evidence indicates that this modulation occurs by the open‐closed gating of individual channels rather than effects on the unitary channel conductance. The precise molecular mechanisms are not yet known, but the functional expression of gap junction proteins should allow for determination of the functional domains responsible for direct and indirect modulation of the cardiac gap junction proteins.
Richard D. Veenstra (Mon,) studied this question.