Micropatterns of propagation.
Alterations in microscopic conduction could contribute to microreentry and arrhythmogenesis in pathological settings. This chapter reviews microconduction in the ventricular myocardium. Gap junctions play a significant role in longitudinal and transverse propagation of the action potential wavefront in the ventricle. Studies of microscopic conduction in patterned cultures of neonatal rodent myocytes have provided novel insights into the role of gap junctions, the effects of uncoupling versus altered excitability, and the contribution of discontinuities and branching. Decreased gap junctional coupling can contribute to slowing of conduction and development of unidirectional block. However, in the setting of structural inhomogeneities and unbalanced current source and load, decreased coupling can, at times, improve conduction and be 'anti-arrhythmic,' attesting to the complexity of intercellular coupling as a therapeutic target. Genetically engineered mouse models of Cx43 depletion demonstrate slow conduction and arrhythmogenesis that appears to be reentrant in nature. Studies in these models provide novel insights into the contribution of gap junctions to impulse propagation and arrhythmogenesis in the intact heart. Overall, gap junction expression, distribution and heterogeneity are important contributors to microscopic conduction, and alterations in any of these can contribute to the development of an arrhythmogenic substrate in pathological states.
Lee
Peter J
PJ
University of Illinois at Chicago, Chicago, Ill., USA.
Pogwizd
Steven M
SM
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000502:physiology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D017629:Gap Junctions / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D006321:Heart / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D013779:Tetrodotoxin / Q000494:pharmacology
D017630:Connexins; D005229:Fatty Acids, Monounsaturated; C008757:palmitoleic acid; D013779:Tetrodotoxin