title: The perinexus: sign-post on the path to a new model of cardiac conduction?
abstract: The perinexus is a recently identified microdomain surrounding the cardiac gap junction that contains elevated levels of connexin43 and the sodium channel protein, Nav1.5. Ongoing work has established a role for the perinexus in regulating gap junction aggregation. However, recent studies have raised the possibility of a perinexal contribution at the gap junction cleft to intercellular propagation of action potential via non-electrotonic mechanisms. The latter possibility could modify the current theoretical understanding of cardiac conduction, help explain paradoxical experimental findings, and open up entirely new avenues for antiarrhythmic therapy. We review recent structural insights into the perinexus and its potential novel functional role in cardiac-excitation spread, highlighting presently unanswered questions, the evidence for ephaptic conduction in the heart and how structural insights may help complete this picture.
authors.affiliation: Department of Surgery, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA.
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Rhett
authors.forename: Rengasayee
authors.initials: R
authors.lastname: Veeraraghavan
authors.forename: Steven
authors.initials: S
authors.lastname: Poelzing
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gourdie
mesh_terms: D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000889:Anti-Arrhythmia Agents; D018031:Connexin 43; D062554:NAV1.5 Voltage-Gated Sodium Channel