Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by decreasing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts
Yeo, Jie Ming
Molecular Medicine Reports
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Tse, G., Yeo, J. M., Tse, V., & Sun, B. (2016). Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by decreasing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff-perfused mouse hearts. Molecular Medicine Reports, 14 (5), 4069-4074. https://doi.org/10.3892/mmr.2016.5738
This is the final version of the article. It first appeared from Spandidos via https://doi.org/ 10.3892/mmr.2016.5738
Arrhythmogenic effects of the gap junction inhibitor heptanol (0.05 mM) were examined in Langendorff-perfused mouse hearts. Monophasic action potential recordings were obtained from the left ventricular epicardium during right ventricular pacing. Regular activity was observed both before and after application of heptanol in all of the 12 hearts studied during 8 Hz pacing. By contrast, induced ventricular tachycardia (VT) was observed after heptanol treatment in 6 out of 12 hearts using a S1S2 protocol (Fisher’s exact test, P < 0.05). The arrhythmogenic effects of heptanol were associated with increased activation latencies from 13.2 ± 0.6 to 19.4 ± 1.3 ms (ANOVA, P < 0.001) and reduced conduction velocities (CVs) from 0.23 ± 0.01 to 0.16 ± 0.01 ms (ANOVA, P < 0.001) in an absence of alterations in action potential durations at x = 90% (38.0 ± 1.0 vs. 38.3 ± 1.8 ms), 70% (16.8 ± 1.0 vs. 19.5 ± 0.9 ms), 50% (9.2 ± 0.8 vs. 10.1 ± 0.6 ms) or 30% (4.8 ± 0.5 vs. 6.3 ± 0.6 ms) repolarization (APDx) or in effective refractory period (ERPs) (39.6 ± 1.9 vs. 40.6 ± 3.0 ms) (all P > 0.05). Consequently, excitation wavelengths (λ, CV x ERP) were reduced from 9.1 ± 0.6 to 6.5 ± 0.6 mm (P < 0.01) but critical intervals for re-excitation (APD90 – ERP) were unaltered (-1.1 ± 2.4 vs. -2.3 ± 1.8 ms; P > 0.05). Together, these findings demonstrate for the first time that inhibition of gap junctions alone using a low heptanol concentration (0.05 mM) was able to reduce CV, which alone was sufficient to permit the induction of VT using premature stimulation by decreasing λ, which therefore appears central in the determination of arrhythmic tendency.
conduction, conduction velocity, repolarization, refractory period, wavelength, gap junction, arrhythmia
GT was awarded a BBSRC Doctoral Training Award at the University of Cambridge.
External DOI: https://doi.org/10.3892/mmr.2016.5738
This record's URL: https://www.repository.cam.ac.uk/handle/1810/256791
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