Premium
Effects of class III antiarrhythmic drugs on the Na + ‐activated K + channels in guinea‐pig ventricular cells
Author(s) -
Mori Katsumi,
Saito Toshihiro,
Masuda Yoshiaki,
Nakaya Haruaki
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15686.x
Subject(s) - amiodarone , antiarrhythmic agent , chemistry , membrane potential , ouabain , myocyte , guinea pig , biophysics , pharmacology , channel blocker , medicine , biochemistry , biology , sodium , atrial fibrillation , heart disease , organic chemistry , calcium
1 Class III antiarrhythmic drugs are known to block the outward currents through voltage‐gated K + channels. However, effects of class III antiarrhythmic drugs on the ligand‐gated K + channels have not been thoroughly examined. In this study effects of amiodarone and newer class III antiarrhythmic drugs, E‐4031 and MS‐551, on the Na + ‐activated K + (K Na ) current were examined in inside‐out membrane patches and in whole cells isolated from guinea‐pig ventricle. 2 The K Na channel current was activated by increasing [Na + ] i from 0 mM to 30–100 mM with 150 mM [K + ] o in inside‐out membrane patches of ventricular myocytes. The channel current showed a larger slope conductance (210 pS), inward‐going rectification and subconductance levels of various amplitudes. 3 E‐4031 and MS‐551 at high concentrations (300 μ m ) inhibited the K + current by decreasing the open time (flickering block). On the other hand, amiodarone at relatively low concentrations (0.1–10 μ m ) inhibited the K Na channel current by decreasing the open probability rather than by decreasing the open time. The IC 50 value of amiodarone for inhibiting the K Na channel current was 1.0 μ m . 4 These drugs also inhibited the whole‐cell outward current activated by intracellular loading of 50 mM [Na + ] i and extracellular application of 10 μ m ouabain. 5 These results indicate that class III antiarrhythmic drugs inhibit the K Na channel current in cardiac cells. However, there are sharp differences in the effective concentrations and the mode of inhibition between amiodarone and the newer class III antiarrhythmic drugs.