Cx43 and Dual-Pathway Electrophysiology of the Atrioventricular Node and Atrioventricular Nodal Reentry

Nikolski, Vladimir P.; Jones, Sandra A.; Lancaster, Matthew K.; Boyett, Mark R.; Efimov, Igor R.

doi:10.1161/01.res.0000059304.97120.2f

Cited by 63 publications

(69 citation statements)

References 39 publications

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“…19 In similar experiments, we observed that in the rat, pacemaker activity at the AV junction also originates in the region of the inferior nodal extension. From the leading pacemaker site, the action potential propagated at a slow velocity (4 to 12 cm/s) along a discrete pathway (the slow pathway) before exiting into the atrial muscle (data not shown).…”

Section: Discussionsupporting

confidence: 59%

Localization of Na ⁺ Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

et al. 2006

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Background-The electrical activity of the atrioventricular node (AVN) is functionally heterogeneous, but how this relates to distinct cell types and the 3-dimensional structure of the AVN is unknown. To address this, we have studied the expression of Na v 1.5 and other Na ϩ channel isoforms in the AVN. Methods and Results-The rat AVN was identified by Masson's trichrome staining together with immunolabeling of marker proteins: connexin40, connexin43, desmoplakin, atrial natriuretic peptide, and hyperpolarization-activated and cyclic nucleotide-gated channel 4. Na ϩ channel expression was investigated with immunohistochemistry with isoform-specific Na ϩ channel antibodies. Na v 1.1 was distributed in a similar manner to Na v 1.5. Na v 1.2 was not detected. Na v 1.3 labeling was present in nerve fibers and cell bodies (but not myocytes) and was abundant in the penetrating atrioventricular (AV) bundle and the common bundle but was much less abundant in other regions. Na v 1.5 labeling was abundant in the atrial and ventricular myocardium and the left bundle branch. Na v 1.5 labeling was absent in the open node, penetrating AV bundle, AV ring bundle, and common bundle but present at a reduced level in the inferior nodal extension and transitional zone. Na v 1.6 was not detected. Conclusions-Our findings provide molecular evidence of multiple electrophysiological cell types at the AV junction.Impaired AV conduction as a result of mutations in or loss of Na v 1.5 must be the result of impaired conduction in the AVN inputs (inferior nodal extension and transitional zone) or output (bundle branches) rather than the AVN itself (open node and penetrating AV bundle).

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Section: Discussionsupporting

confidence: 59%

Localization of Na ⁺ Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

et al. 2006

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“…Optical and multielectrode mapping data in a rabbit model have suggested that perinodal atrial tissue participates in the reentrant circuit. [11][12][13] We hypothesize that the AVR could form these inputs to the AV node, which in turn could serve in the adult as part of the perinodal reentrant circuit during AVNRT.…”

Section: Discussionmentioning

confidence: 99%

Atrioventricular Ring Reentry in Embryonic Mouse Hearts

et al. 2006

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Background-During development, AV conduction switches from base-to-apex to apex-to-base conduction after emergence of the conduction system. We hypothesize that after this transition, the bulk of the AV ring, although no longer required for AV conduction, remains transiently able to conduct, providing a potential arrhythmia substrate. We studied AV conduction during this transition and its sensitivity to autonomic modulation. Methods and Results-Simultaneous voltage and Ca2ϩ mapping with RH-237 and Rhod-2 was performed with 2 CCD cameras in embryonic mouse hearts (nϭ43). Additionally, isolated calcium mapping was performed in 309 hearts with fluo-3AM. Propagation patterns in voltage and Ca 2ϩ mapping coincided. Arrhythmias were uncommon under basal conditions, with AV block in 14 (4%) and junctional rhythms in 4 (1%). Arrhythmias increased after stimulation with isoproterenol-junctional rhythm in 9 (3%) and ventricular rhythms in 22 (6%)-although AV block decreased (3 hearts, 1%). Adding carbachol after isoproterenol caused dissociated antegrade and retrograde AV ring conduction in 30 (8.6%) of E10.5 and E11.5 hearts, occurring preferentially in the right and left sides of the ring, respectively. In 2 cases, reentry occurred circumferentially around the AV ring, perpendicular to normal propagation. Reentry persisted for multiple beats, lasting from 3 to 22 minutes. No episodes of AV ring reentry occurred in E9.5 hearts. Conclusions-AV ring reentry can occur by spatial dissociation of antegrade and retrograde conduction during combined adrenergic and muscarinic receptor stimulation. Critical maturation (ϾE9.5) seems to be required to sustain reentry.

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“…Cx43 is the main constituent of the majority of gap junction channels connecting ventricular myocytes. It can be visualized by immunolabeling, which has been described previously (6,35). Briefly, a commercially available anti-Cx43 monoclonal antibody raised in mouse (catalog no.…”

Section: Methodsmentioning

confidence: 99%

Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage

Sambelashvili

Nikolski

Efimov

2004

American Journal of Physiology-Heart and Circulatory Physiology

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The virtual electrode polarization (VEP) effect is believed to play a key role in electrical stimulation of heart muscle. However, under certain conditions, including clinically, its existence and importance remain unknown. We investigated the influence of acute tissue damage produced by continuous pacing with strong current (40-mA, 4-ms biphasic pulses with 4-Hz frequency for 5 min) on stimulus-generated VEPs and pacing thresholds. A fluorescent optical mapping technique was used to obtain stimulus-induced transmembrane potential distribution around a pacing electrode applied to the ventricular surface of a Langendorff-perfused rabbit heart ( n = 5). Maps and pacing thresholds were recorded before and after tissue damage. Spatial extents of electroporation and cell uncoupling were assessed by propidium iodide ( n = 2) and connexin43 ( n = 3) antibody staining, respectively. On the basis of these data, passive and active three-dimensional bidomain models were built to determine VEP patterns and thresholds for different-sized areas of the damaged region. Electrophysiological results showed that acute tissue damage led to disappearance of the VEP with an associated significant increase in pacing thresholds. Damage was expressed in electroporation and cell uncoupling within a ∼1.0-mm-diameter area around the tip of the electrode. According to computer simulations, cell uncoupling, rather than electroporation, might be the direct cause of VEP elimination and threshold increase, which was nonlinearly dependent on the size of the damaged region. Fiber rotation with depth did not substantially affect the numerical results. The study explains failure to stimulate damaged tissue within the concepts of the VEP theory.

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Cx43 and Dual-Pathway Electrophysiology of the Atrioventricular Node and Atrioventricular Nodal Reentry

Cited by 63 publications

References 39 publications

Localization of Na ⁺ Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

Localization of Na ⁺ Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

Atrioventricular Ring Reentry in Embryonic Mouse Hearts

Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage

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Cx43 and Dual-Pathway Electrophysiology of the Atrioventricular Node and Atrioventricular Nodal Reentry

Cited by 63 publications

References 39 publications

Localization of Na + Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

Localization of Na + Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

Atrioventricular Ring Reentry in Embryonic Mouse Hearts

Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage

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Localization of Na ⁺ Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat

Localization of Na ⁺ Channel Isoforms at the Atrioventricular Junction and Atrioventricular Node in the Rat