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Acta Physiol (Oxf). 2013 Feb;207(2):280-9. doi: 10.1111/j.1748-1716.2012.02481.x. Epub 2012 Sep 14.

Potassium channel activators differentially modulate the effect of sodium channel blockade on cardiac conduction.

Author information

1
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112, USA.

Abstract

AIMS:

Diminished repolarization reserve contributes to the arrhythmogenic substrate in many disease states. Pharmacological activation of K(+) channels has been suggested as a potential antiarrhythmic therapy in such conditions. Having previously demonstrated that I(K1) and I(Kr) can modulate cardiac conduction, we tested here the effects of pharmacological I(KATP) and I(Ks) activation on cardiac conduction and its dependence on the sodium current (I(Na)).

METHODS AND RESULTS:

Bath electrocardiograms (ECGs) recorded from Langendorff-perfused guinea pig ventricles revealed QRS prolongation during I(KATP) activation by pinacidil but not during I(Ks) activation by R-L3 relative to control. In contrast, when I(Na) was partially blocked by flecainide, R-L3 but not pinacidil prolonged the QRS relative to flecainide alone. Conduction velocity (θ) was quantified by optical mapping during epicardial pacing. Both longitudinal (θ(L)) and transverse (θ(T)) θ were reduced by pinacidil (by 10 ± 1 and 9 ± 3%, respectively) and R-L3 (by 11 ± 2% and 15 ± 4%, respectively). Flecainide decreased θ(L) by 33 ± 4% and θ(T) by 36 ± 5%. Whereas pinacidil did not further slow θ relative to flecainide alone, R-L3 decreased both θ(L) and θ(T).

CONCLUSION:

Pharmacological activation of I(KATP) and I(Ks) slows cardiac conduction; however, they demonstrate diverse effects on θ dependence on I(Na) blockade. These findings may have significant implications for the use of K(+) channel activators as antiarrhythmic drugs and for patients with Na(+) channel abnormalities or being treated with Na(+) channel blockers.

PMID:
22913299
PMCID:
PMC3980511
DOI:
10.1111/j.1748-1716.2012.02481.x
[Indexed for MEDLINE]
Free PMC Article
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