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Electrophysiological effects of diclofurime on rabbit and frog atrial heart muscle
Author(s) -
Gautier Patrick,
Guiraudou Pierre,
Sauviat MartinPierre
Publication year - 1987
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.1476-5381.1987.tb11225.x
Subject(s) - sucrose gap , depolarization , electrophysiology , chemistry , membrane potential , biophysics , voltage clamp , resting potential , medicine , sodium , dissociation constant , sinoatrial node , conductance , sodium channel , reversal potential , endocrinology , anatomy , patch clamp , biology , biochemistry , heart rate , receptor , mathematics , organic chemistry , combinatorics , blood pressure
1 The effects of diclofurime on the electrical activity of the rabbit sinus node, rabbit atria and frog atrial fibres were studied using microelectrode and the double sucrose gap voltage‐clamp techniques respectively. 2 In rabbit sinus node, diclofurime (10 −7 m to 10 −6 m ) decreased the action potential (AP) amplitude and maximum rate of depolarization , increased the AP duration and slowed the sinus rate. 3 In rabbit atria, the drug reduced the amplitude of the depolarizing phase and , lengthened the AP duration and decreased the resting membrane potential. 4 In frog atrial fibres, the drug (10 −5 m ) depolarized the resting membrane potential, decreased as well as the plateau amplitude. It inhibited the sodium current ( I Na ) with a dissociation constant of 3.7 × 10 −6 M and a one to one relationship between the drug molecule and the Na channel. Diclofurime did not alter the apparent reversal potential for the fast Na current (E Na ) but it inhibited the sodium conductance ( G Na ) in a frequency‐dependent manner. 5 Diclofurime also blocked the slow inward current ( I slow ) without alteration of E slow . The block of I slow occurred with a dissociation constant of 2 × 10 −5 m and unity stoichiometry. 6 The data suggest that diclofurime might be effective in the control of cardiac arrythmias since it exhibited both local anaesthetic‐like and calcium antagonistic properties.