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The effect of TYB‐3823, a new antiarrhythmic drug, on sodium current in isolated cardiac cells
Author(s) -
Miyamoto Jiro,
Hisatome Ichiro,
Matsuoka Satoshi,
Kosaka Hiromoto,
Kurata Yasutaka,
Tanaka Yasunori,
Nawada Takahiro,
Kotake Hiroshi,
Mashiba Hiroto,
Sato Ryoichi
Publication year - 1991
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.1476-5381.1991.tb12379.x
Subject(s) - sodium channel , sodium , blockade , chemistry , tonic (physiology) , block (permutation group theory) , patch clamp , pharmacology , biophysics , electrophysiology , steady state (chemistry) , anesthesia , receptor , medicine , biochemistry , biology , mathematics , geometry , organic chemistry
1 Sodium current ( I Na ) blockade by TYB‐3823, a newly synthesized antiarrhythmic agent, was investigated in isolated single ventricular myocytes by use of the whole cell patch‐clamp technique. 2 TYB‐3823 blocked I Na under steady‐state conditions ( K d, rest = 500 μ m , K d, i = 4.9 μ m ), findings consistent with a shift in the steady state I Na availability curve to more negative potentials. 3 TYB‐3823 produced use‐dependent block at 2 Hz in conjunction with increase in pulse duration (5–300 ms), that was markedly enhanced at less negative holding potentials. 4 The time course of the onset of block was accelerated and the degree of use‐dependent block was decreased at more negative holding potential. The time course of the onset of block was accentuated with enhancing block at more positive holding potentials. 5 The time course of recovery from use‐dependent block was accelerated at more negative holding potentials but was accentuated at more positive holding potentials. 6 These results suggest that both tonic block and use‐dependent block of sodium channels in cardiac tissue might result from an interaction of TYB‐3832 with sodium channels mainly in the inactivated channel states and the kinetics of the interaction between drug and receptor may be modulated by the inactivation gate.