Inhibition of the Na,K‐ATPase by the Antiarrhythmic Drug, Bretylium

Gatto, Craig; Barkulis, Charles T.; Schneider, W.; Holden, Jeremy P.; Arnett, Krista L.; Milanick, Mark A.

doi:10.1111/j.1749-6632.2003.tb07265.x

Cited by 2 publications

(1 citation statement)

References 3 publications

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“…This finding may have implications for our understanding of the antiarrhythmic effect of adenosine when used clinically. The inhibition of Na + -K + pump prolongs action potential duration and myocardial refractoriness, which is involved in the mechanisms of two other widely used antiarrhythmic agents, bretylium and amiodarone [33,34] . Thus, it is tempting to speculate that the antiarrhythmic effects of adenosine are in part caused by Na + -K + pump inhibition.…”

Section: Discussionmentioning

confidence: 99%

Isoform-specific regulation of the Na+-K+ pump by adenosine in guinea pig ventricular myocytes

et al. 2009

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Aim: The present study investigated the effect of adenosine on Na + -K + pumps in acutely isolated guinea pig (Cavia sp.) ventricular myocytes. Methods: The whole-cell, patch-clamp technique was used to record the Na + -K + pump current (I p ) in acutely isolated guinea pig ventricular myocytes. Results: Adenosine inhibited the high DHO-affinity pump current (I h ) in a concentration-dependent manner, which was blocked by the selective adenosine A 1 receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists staurosporine, GF 109203X or the specific δ isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A 1 receptor agonist CCPA and a specific activator peptide of PKC-δ, PP114. In contrast, the selective A 2A receptor agonist CGS21680 and A 3 receptor agonist Cl-IB-MECA did not affect I h . Application of the selective A 2A receptor antagonist SCH58261 and A 3 receptor antagonist MRS1191 also failed to block the effect of adenosine. Furthermore, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced I h inhibition. Conclusion:The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of I h via adenosine A 1 receptors and the PKC-δ isoform.

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Section: Discussionmentioning

confidence: 99%