1. We investigated the effects of JTV-519 
(4-[3-(4-benzylpiperidin-1-yl)propionyl]-7-methoxy-2,3,4, 
5-tetrahydro-1,4-benzothiazepine monohydrochloride), a novel cardioprotective 
drug, on the repolarizing K(+) currents in guinea-pig atrial cells by use of 
patch-clamp techniques. We also evaluated the effects of JTV-519 on experimental 
atrial fibrillation (AF) in isolated guinea-pig hearts. 2. In atrial cells 
stimulated at 0.2 Hz, JTV-519 in concentrations of 0.3 and 1 microM slightly 
prolonged the action potential duration (APD). The drug also reversed the action 
potential shortening induced by the muscarinic agonist carbachol in a 
concentration-dependent manner. 3. The muscarinic acetylcholine 
receptor-operated K(+) current (I(K.ACh)) was activated by the extracellular 
application of carbachol (1 microM), adenosine (10 microM) or by the 
intracellular loading of GTP gamma S (100 microM). JTV-519 inhibited the 
carbachol-, adenosine- and GTP gamma S-induced I(K.ACh) with the IC(50) values 
of 0.12, 2.29 and 2.42 microM, respectively, suggesting that the drug may 
inhibit I(K.ACh) mainly by blocking the muscarinic receptors. 4. JTV-519 (1 
microM) inhibited the delayed rectifier K(+) current (I(K)). 
Electrophysiological analyses indicated that the drug preferentially inhibits 
I(Kr) (rapidly activating component) but not I(Ks) (slowly activating 
component). 5. In isolated hearts, perfusion of carbachol (1 microM) shortened 
monophasic action potential (MAP) and effective refractory period (ERP), and 
lowered atrial fibrillation threshold (AFT). Addition of JTV-519 (1 microM) 
inhibited the induction of AF by prolonging MAP and ERP. 6. We conclude that 
JTV-519 can exert antiarrhythmic effects against AF by inhibiting repolarizing 
K(+) currents. The drug may be useful for the treatment of AF in patients with 
ischaemic heart disease.