Aconitine-induced delayed afterdepolarization in frog atrium and guinea pig papillary muscles in the presence of low concentrations of Ca2+.
Aconitine will induce arrhythmias after the fiber has been completely repolarized. This arrhythmia is generally facilitated in the presence of high Ca2+ solution, yet the aconitine-induced arrhythmia occurs even in the presence of low Ca2+ solutions. We studied aconitine-induced arrhythmia (particularly the amplitude of delayed afterdepolarization) in the frog atrium or guinea-pig papillary muscles in Ca2+-free solution, in the presence or absence of Ca2+ channel blocking agents. In Ca2+-free solution, aconitine (10(-5) g/ml) decreased the resting potential, overshoot, Vmax, and shortened the duration of the 90% action potential, before the onset of delayed afterdepolarization in frog atrial preparations. Tetrodotoxin (TTX) (2 X 10(-7) g/ml) blocked these aconitine-induced electrical changes. Verapamil (10(-6) g/ml) in nominally Ca2+-free solution blocked neither the generation of delayed afterdepolarization nor the triggered activity, while LaCl3 (0.5 mM) or TTX halted it. Delayed afterdepolarization appeared following the aconitine-induced transient increase in twitch tension. This transient increase in twitch tension was blocked by LaCl3 and TTX but not by verapamil. Delayed afterdepolarization in Ca2+-free solution demonstrated the voltage dependence of a U shape between -40 and -80 mV and was inhibited by low Na+ and high K+. Under the influence of aconitine in the guinea pig papillary muscle exposed to the Ca2+-free solution, depolarizing clamp pulses produced a transient inward current, and here the sigmoid time- and voltage-dependent characteristics were similar to those seen in the case of digitalis intoxication. These results suggest that intracellular Na+ loading plays an important role in the aconitine-induced delayed afterdepolarization and transient inward currents in low Ca2+ solution.
D000157:Aconitine / Q000494:pharmacology*; D031841:Aconitum / Q000031:analogs & derivatives*; D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D011892:Rana catesbeiana; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013779:Tetrodotoxin; D002118:Calcium; D000157:Aconitine