Isopimaric acid – a multi‐targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line

Abstract

Low concentrations of IPA reduced the action potential frequency and restored regular firing by altering the voltage dependencies of several voltage-gated ion channels. These findings can form the basis for a new pharmacological strategy to treat atrial fibrillation.

Can principles of the surface potential be combined with knowledge of natural products to reduce atrial rhythm disturbances?

“…The data in panel (e) were computed based on a combination of all of these isopimaric acid‐induced changes. Note that these changes are still prominent after the two K + currents, I to and IKr, that strongly regulate repolarization are modified in accordance with the findings of Salari et al …”

“…Although both paroxysmal (brief) and chronic atrial fibrillation (AF) were considered to be benign, the notable association between maintained AF and stroke has resulted in AF now being a target for surgical intervention (ablation) and/or drug therapy. An interesting, forward‐looking paper from the Elinder group in this issue of Acta Physiologica reveals novel pharmacological agents and principles that could be the basis for more effective antiarrhythmic therapies for AF. Salari et al .…”

“…An interesting, forward‐looking paper from the Elinder group in this issue of Acta Physiologica reveals novel pharmacological agents and principles that could be the basis for more effective antiarrhythmic therapies for AF. Salari et al . rigorously evaluate the possibility that altering the activity of not one, but several different transmembrane ionic currents that are essential for generation of the atrial action potential can reduce spontaneous firing and prolong the action potential.…”

“…Salari et al . accomplish this by utilizing a surrogate for a mouse atrial myocyte (HL‐1 cells) in culture and applying selected natural compounds (resin acids) that they have previously studied in other model systems .…”

Sodium Houttuyfonate Inhibits Voltage-Gated Peak Sodium Current and Anemonia Sulcata Toxin II-Increased Late Sodium Current in Rabbit Ventricular Myocytes

“…SH accelerated the steady state inactivation of I Na.P , indicating that SH reduced sodium channel availability as well as cardiomyocyte excitability [16,17]. Furthermore, it has been reported that many tachyarrhythmias, such as atrial fibrillation, were often accompanied by increased myocardial excitability, suggesting that the sodium channel may be an effective target for treating such tachyarrhythmias [18,19]. Thus, the reduced sodium channel availability by SH revealed that SH possessed great possibility to alleviate atrial fibrillation.…”