title: Mechanism of delayed afterdepolarization caused by aconitine.
abstract: In an investigation of the mechanism of action of delayed afterdepolarizations (DAD) effects of aconitine (A) on sodium (INa), calcium (ICa), and outward (Iout), currents in frog atrium under double sucrose gap conditions were studied. Some of the fast sodium channels were modified by A (5 X 10(-5) g/ml, 5 min) so that the rate of inactivation decreased and activation was shifted by 15.7 +/- 4.5 mV (mean +/- S.E., N = 9) to more negative potentials. Maximum sodium conductance (gNa) decreased to 69 +/- 14% (N = 7), and the conductance of the modified channels was 4 +/- 2.3% (N = 7) of the control value of gNa at potentials 8 mV more negative than the threshold for the fast INa. The reversal potential of INa was shifted to more negative potentials. Oscillations of the modified inward current at fixed potentials were observed. Tetrodotoxin (10(-6) M) completely inhibited both the normal and modified currents and the current oscillations (CO). After 10 min of A (10(-4) g/ml) action, ICa diminished reversibly to 65 +/- 11% (N = 9) of control value; no changes in Iout were observed. It was supposed that DAD were caused by continuous uptake of Na+ by the cells through the modified channels, leading to an increase in the intracellular Ca2+ concentration and that interaction of Ca2+ with modified channels causes the current oscillations.
mesh_terms: D000157:Aconitine / Q000494:pharmacology*; D031841:Aconitum / Q000031:analogs & derivatives*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004562:Electrocardiography; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D011895:Rana ridibunda; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D002118:Calcium; D000157:Aconitine