Site of origin and molecular substrate of atrioventricular junctional rhythm in the rabbit heart.
During failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker. The position of the leading pacemaker site during AV junctional rhythm is debated. In this study, we present evidence from high-resolution fluorescent imaging of electrical activity in rabbit isolated atrioventricular node (AVN) preparations that, in the majority of cases (11 out of 14), the AV junctional rhythm originates in the region extending from the AVN toward the coronary sinus along the tricuspid valve (posterior nodal extension, PNE). Histological and immunohistochemical investigation showed that the PNE has the same morphology and unique pattern of expression of neurofilament160 (NF160) and connexins (Cx40, Cx43, and Cx45) as the AVN itself. Block of the pacemaker current, If, by 2 mmol/L Cs+ increased the AV junctional rhythm cycle length from 611+/-84 to 949+/-120 ms (mean+/-SD, n=6, P<0.001). Immunohistochemical investigation showed that the principal If channel protein, HCN4, is abundant in the PNE. As well as the AV junctional rhythm, the PNE described in this study may also be involved in the slow pathway of conduction into the AVN as well as AVN reentry, and the predominant lack of expression of Cx43 as well as the presence of Cx45 in the PNE shown could help explain its slow conduction.
Dobrzynski
Halina
H
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
Nikolski
Vladimir P
VP
Sambelashvili
Alexandre T
AT
Greener
Ian D
ID
Yamamoto
Mitsuru
M
Boyett
Mark R
MR
Efimov
Igor R
IR
D000818:Animals; D016275:Atrial Function / Q000187:drug effects / Q000502:physiology; D001283:Atrioventricular Node / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D018780:Body Surface Potential Mapping; D002586:Cesium / Q000494:pharmacology; D018031:Connexin 43 / Q000032:analysis; D017630:Connexins / Q000096:biosynthesis; D054815:Cyclic Nucleotide-Gated Cation Channels; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D016900:Neurofilament Proteins / Q000096:biosynthesis; D055095:Optics and Photonics; D010507:Periodicity; D015221:Potassium Channels; D011726:Pyridinium Compounds; D011817:Rabbits; D012849:Sinoatrial Node / Q000502:physiology; D000097003:Gap Junction alpha-5 Protein
D002586:Cesium; D018031:Connexin 43; D017630:Connexins; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; D016900:Neurofilament Proteins; D015221:Potassium Channels; D011726:Pyridinium Compounds; D000097003:Gap Junction alpha-5 Protein; C119587:HCN4 protein, human; C082920:connexin 45; C050019:1-(3-sulfonatopropyl)-4-(beta)(2-(di-n-butylamino)-6-naphthylvinyl)pyridinium betaine