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Effects of dronedarone on Acetylcholine‐activated current in rabbit SAN cells
Author(s) -
Altomare Claudia,
Barbuti Andrea,
Viscomi Carlo,
Baruscotti Mirko,
DiFrancesco Dario
Publication year - 2000
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 - 10.1038/sj.bjp.0703446
Subject(s) - dronedarone , acetylcholine , muscarinic acetylcholine receptor , chemistry , biophysics , pharmacology , gtp' , sinoatrial node , medicine , receptor , biochemistry , biology , atrial fibrillation , amiodarone , enzyme , heart rate , blood pressure
The effect of the antiarrhythmic drug dronedarone on the Acetylcholine‐activated K + current ( I K(ACh) ) was investigated in single cells isolated from sinoatrial node (SAN) tissue of rabbit hearts. Externally perfused dronedarone (0.001–1 μ M ) caused a potent, voltage independent block of I K(ACh) . Fitting of the dose response curve of I K(ACh) block yielded an IC 50 value of 63 n M , a value over one order of magnitude lower than those reported for dronedarone block of other cardiac currents.I K(ACh) block was not due to an inhibitory action of dronedarone on the muscarinic M2 receptor activation, since the drug was effective on I K(ACh) constitutively activated by intracellular perfusion with GTP‐γS. External cell perfusion with dronedarone inhibited the activity of I K(ACh) channels recorded from cell‐attached patches by reducing the channel open probability (from 0.56 to 0.11) without modification of the single‐channel conductance. These data suggest that dronedarone blocks I K(ACh) channels either by disrupting the G‐protein‐mediated activation or by a direct inhibitory interaction with the channel protein.British Journal of Pharmacology (2000) 130 , 1315–1320; doi: 10.1038/sj.bjp.0703446