Functional roles of a Ca2+ -activated K+ channel in atrioventricular nodes

Qian Zhang, Valeriy Timofeyev, Ling Lu, Ning Li, Anil Singapuri, Melissa K. Long, Chris T. Bond, John P. Adelman, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Since the first description of the anatomical atrioventricular nodes (AVNs), a large number of studies have provided insights into the heterogeneity of the structure as well as a repertoire of ion channel proteins that govern this complex conduction pathway between the atria and ventricles. These studies have revealed the intricate organization of multiple nodal and nodal-like myocytes contributing to the unique electrophysiology of the AVN in health and diseases. On the other hand, information regarding the contribution of specific ion channels to the function of the AVN remains incomplete. We reason that the identification of AVN-specific ion channels may provide a more direct and rational design of therapeutic target in the control of AVN conduction in atrial flutter/fibrillation, one of the most common arrhythmias seen clinically. In this study, we took advantage of 2 genetically altered mouse models with overexpression or null mutation of 1 of a small conductance Ca-activated K channel isoform, SK2 channel, and demonstrated robust phenotypes of AVN dysfunction in these experimental models. Overexpression of SK2 channels results in the shortening of the spontaneous action potentials of the AVN cells and an increase in the firing frequency. On the other hand, ablation of the SK2 channel results in the opposite effects on the spontaneous action potentials of the AVN. Furthermore, we directly documented the expression of SK2 channel in mouse AVN using multiple techniques. The new insights may have important implications in providing novel drug targets for the modification of AVN conduction in the treatment of atrial arrhythmias.

Original languageEnglish (US)
Pages (from-to)465-471
Number of pages7
JournalCirculation Research
Volume102
Issue number4
DOIs
StatePublished - Feb 2008

Fingerprint

Calcium-Activated Potassium Channels
Atrioventricular Node
Ion Channels
Action Potentials
Cardiac Arrhythmias
Atrial Flutter
Electrophysiology
Atrial Fibrillation
Muscle Cells
Protein Isoforms
Theoretical Models
Phenotype

Keywords

  • Atrioventricular nodes
  • K2.2 channel
  • SK2 channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Functional roles of a Ca2+ -activated K+ channel in atrioventricular nodes. / Zhang, Qian; Timofeyev, Valeriy; Lu, Ling; Li, Ning; Singapuri, Anil; Long, Melissa K.; Bond, Chris T.; Adelman, John P.; Chiamvimonvat, Nipavan.

In: Circulation Research, Vol. 102, No. 4, 02.2008, p. 465-471.

Research output: Contribution to journalArticle

Zhang, Q, Timofeyev, V, Lu, L, Li, N, Singapuri, A, Long, MK, Bond, CT, Adelman, JP & Chiamvimonvat, N 2008, 'Functional roles of a Ca2+ -activated K+ channel in atrioventricular nodes', Circulation Research, vol. 102, no. 4, pp. 465-471. https://doi.org/10.1161/CIRCRESAHA.107.161778
Zhang, Qian ; Timofeyev, Valeriy ; Lu, Ling ; Li, Ning ; Singapuri, Anil ; Long, Melissa K. ; Bond, Chris T. ; Adelman, John P. ; Chiamvimonvat, Nipavan. / Functional roles of a Ca2+ -activated K+ channel in atrioventricular nodes. In: Circulation Research. 2008 ; Vol. 102, No. 4. pp. 465-471.
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