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Mechanical and electrophysiological studies on the positive inotropic effect of 2‐phenyl‐4‐oxo‐hydroquinoline in rat cardiac tissues
Author(s) -
Su Ming Jai,
Chang Gwo Jyh,
Kuo Sheng Chu
Publication year - 1993
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.1476-5381.1993.tb13810.x
Subject(s) - verapamil , electrophysiology , inotrope , medicine , channel blocker , cardiac transient outward potassium current , endocrinology , cardiac action potential , chemistry , sodium channel , biophysics , patch clamp , pharmacology , sodium , calcium , biology , repolarization , organic chemistry
1 The pharmacological and electrophysiological effect of 2‐phenyl‐4‐oxo‐hydroquinoline (YT‐1), a new synthetic agent, were determined in rat isolated cardiac tissues and ventricular myocytes. 2 YT‐1 was found to have a positive inotropic effect in both atria and ventricular muscles but did not cause significant increases in the spontaneously beating rate of right atria. 3 The positive inotropic effect of YT‐1 was antagonized neither by β‐nor by α‐adrenoceptor antagonists but was partially antagonized by a Ca 2+ channel blocker (verapamil) and a K + channel blocker (4‐AP). 4 The action potential duration and amplitude of ventricular cells were progressively increased as the concentration of YT‐1 was increased from 3 to 30 μ m . 5 A voltage clamp study revealed that the prolongation of action potential duration by YT‐1 was associated with a prominent inhibition of 4‐AP‐sensitive transient outward current ( I to ). At potentials negative to the reversal potential of K 1 ‐channels, the inward current through these channels was partially reduced by YT‐1. At potentials positive to the reversal potential, the outward current through these channels was affected very little. 6 Although YT‐1 blocked the amplitude of I to , the voltage‐dependence of the steady‐state inactivation of I to , was unaffected. 7 Apart from the inhibition of K + currents, YT‐1 also inhibited the sodium inward current. 8 The evidence suggests that YT‐1 increases the slow inward Ca 2+ current ( I Ca ) significantly. 9 It is concluded that the positive inotropic effect of YT‐1 is due predominantly to the increase of I Ca and inhibition of I to .