Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hirose, M. et al.

Effect of nifekalant, a class III anti-arrhythmic agent, on Ca2+ waves in rat intact trabeculae.

BACKGROUND: Nifekalant, a class III anti-arrhythmic agent, has been used clinically at serum concentrations of 1-10 micromol/L in patients with ventricular arrhythmias. However, the effect of nifekalant on triggered arrhythmias has not yet been established. METHODS AND RESULTS: Trabeculae were dissected from the right ventricles of 16 rat hearts. The force was measured using a silicon strain gauge, the membrane potential using ultra-compliant microelectrodes, and the regional intracellular Ca2+ ([Ca2+]i) using electrophoretically microinjected fura-2 and an image intensified CCD camera at a sarcomere length of 2.1 microm. Rapid cooling contractures (RCCs) were measured to estimate the Ca2+ content in the sarcoplasmic reticulum. Ca2+ waves and aftercontractions were measured after the induction of reproducible Ca2+ waves. Nifekalant at 1, 10 and 250 micromol/L increased significantly the action potential duration, the peak [Ca2+]i, the developed force and the amplitude of RCCs in a concentration-dependent manner (stimulus interval = 2 s, [Ca2+]o = 0.7 mmol/L, 26.0+/-0.2 degrees C). Nifekalant at 10 and 250 micromol/L increased significantly the velocity of Ca2+ waves with an enhancement of the aftercontractions (stimulus interval = 0.5 s for 7.5 s, [Ca2+]o = 1.8+/-0.1 mmol/L, 22.3+/-0.5 degrees C). CONCLUSIONS: Nifekalant, even at a therapeutic concentration, can increase muscle contraction, but may worsen triggered arrhythmias because of the acceleration of Ca2+ waves under Ca2+-overloaded conditions.[1]

References

Effect of nifekalant, a class III anti-arrhythmic agent, on Ca2+ waves in rat intact trabeculae. Hirose, M., Miura, M., Wakayama, Y., Endo, H., Sugai, Y., Stuyvers, B.D., Kagaya, Y., Watanabe, J., ter Keurs, H.E., Shirato, K. Circ. J. (2005) [Pubmed]

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