Activation of Glibenclamide-Sensitive ATP-Sensitive K+ Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia

Shang Jin Kim, Haifei Zhang, Igor Khaliulin, Stephanie C M Choisy, Richard C Bond, Hua Lin, Said El Haou, James T Milnes, Jules C Hancox, M.S. Suleiman, Andrew F James

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Citations (Scopus)

Abstract

Background: Cardiac ATP-sensitive K+ (KATP) channels have been suggested to contribute to the adaptive physiological response to metabolic challenge following ß-adrenoceptor stimulation. However, an increased atrial K+-conductance might be expected to be pro-arrhythmic. We investigated the effect of KATP channel blockade on the electrophysiological responses to ß-adrenoceptor-induced metabolic challenge in intact atria.
Methods: Atrial electrograms were recorded from the left atrial epicardial surface of Langendorff-perfused rat hearts using a 5×5 electrode array. Atrial effective refractory period (AERP) and conduction velocity (CV) were measured using an S1-S2 protocol. The proportion of hearts in which atrial tachyarrhythmia (AT) was produced by burst-pacing was used as an index of AT-inducibility. Atrial nucleotide concentrations were measured by HPLC.
Results: Perfusion with ≥10-9 M of the ß-adrenoceptor agonist, isoproterenol (ISO), resulted in a concentration-dependent reduction of AERP and CV. The ISO-induced changes produced a pro-arrhythmic substrate such that AT could be induced by burst-pacing. Atrial [ATP] was significantly reduced by ISO (10-6 M). Perfusion with either of the KATP channel blockers, glibenclamide (10-5 M) or tolbutamide (10-3 M) in the absence of ISO had no effect on basal atrial electrophysiology. On the other hand, the pro-arrhythmic substrate induced by 10-6 M ISO was abolished by either of the sulfonylureas, which prevented induction of AT.
Conclusion: Atrial KATP channels activate in response to ß-adrenergic metabolic stress in Langendorff-perfused rat hearts, resulting in a pro-arrhythmic substrate.

Original languageEnglish
Pages (from-to)1184-1192
JournalCirculation: Arrhythmia and Electrophysiology
Volume5
Issue number6
Early online date16 Nov 2012
DOIs
Publication statusPublished - 2012

Keywords

  • arrhythmia, ATP-sensitive K+ channel, atrial fibrillation, reentry, sulphonylurea

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