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Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells
Author(s) -
Bois Patrick,
Bescond Jocelyn,
Renaudon Barbara,
Lenfant Jacques
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.tb15505.x
Subject(s) - diastolic depolarization , sinoatrial node , chemistry , repolarization , patch clamp , medicine , depolarization , pacemaker potential , endocrinology , inotrope , calcium , biophysics , bradycardia , heart rate , electrophysiology , biology , blood pressure
1 The effect of the bradycardic agent S 16257 on the main ionic mechanisms of diastolic depolarization in sinoatrial node cells isolated from rabbit heart, was investigated by the patch‐clamp technique in whole‐cell and macro‐patch recordings. 2 In whole‐cell conditions, S 16257 induced a marked exponential use‐dependent blockade of the hyperpolarization‐activated I f current, without shift of the voltage range of its activation curve. The rate of block increased with the drug concentration. The IC 50 for the block of I f was 2.8 × 10 −6 m . 3 A similar use‐dependent decline of I f was obtained with 3 μ m S 16257, in cell‐attached and in inside‐out macro‐patch configurations, suggesting that the bradycardic agent interacts with I f channels from the inside of the cell. 4 A high concentration of S 16257 (10 μ m ) had no detectable effect on T‐type calcium current and slightly decreased L‐type calcium current (−18.12±0.66%), without significant use‐dependent blockade. 5 S 16257 had no effect on the delayed outward potassium current I K at 3 μ m and slightly decreased it only at high concentrations, −16.3±1.2% at 10 μ m . In contrast, zatebradine, another bradycardic agent, reduced I K by 20.3±2.5% at 3 μ m . 6 In conclusion, S 16257 may lower heart rate without significant negative inotropic action. In comparison with zatebradine, S 16257 had less effect on I K suggesting less prolongation of repolarization time.