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Mechanical and electrophysiological effects of 8‐oxoberberine (JKL1073A) on atrial tissue
Author(s) -
Chi JoFeng,
Chu ShuHsun,
Lee ChihShone,
Chou NaiKaun,
Su MingJai
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.tb15431.x
Subject(s) - chronotropic , electrophysiology , atrium (architecture) , medicine , chemistry , endocrinology , prazosin , inotrope , patch clamp , dissociation constant , voltage clamp , antagonist , atrial fibrillation , heart rate , receptor , blood pressure
1 The effects of 8‐oxoberberine (JKL1073A) on contractions and electrophysiological characteristics of atrial tissues were examined. 2 In driven left atria of the rat JKL1073A (10–100 μ m ) increased twitch tension dose‐dependently. In spontaneously beating right atria, JKL1073A increased twitch tension but decreased beating rate slightly. 3 The positive inotropic and the negative chronotropic effect of 30 μ m JKL1073A was not affected by prazosin (1 μ m ), propranolol (1 μ m ) and 3‐isobutyl‐1‐methyl‐xanthine (10 μ m ) but significantly suppressed by 4‐aminopyridine (2 mM 4‐AP). 4 Current‐clamp study revealed that JKL1073A prolonged rat atrial action potential duration (APD). This prolongation of APD by JKL1073A was decreased by pretreating the cells with 2 mM 4‐AP. Voltage‐clamp study showed that JKL1073A inhibited the integral of the transient outward current ( I to ) dose‐dependently with a K D value of 3.66 ± 0.93 μ m in rat atrial myocytes. The equilibrium dissociation constant ( K d ) for JKL1073A bindings to open state I to was 0.50 ± 0.08 μ m . The suppression of I to by 3 μ m JKL1073A was accompanied by shortening of its inactivation time constant from 52.5 ± 0.9 ms to 16.8 ± 0.7 ms. V 0.5 for the steady‐state inactivation curve of I to was shifted from −25.7 ± 3.3 mV to −34.8 ± 3.2 mV. 5 In human atrial cells, similar inhibition of I to and prolongation of APD by JKL1073A was found. The K D value of JKL1073A for inhibition of the integral of I to in human atrial cells is 4.03 ± 0.02 μ m . The K d for bindings to open state I to is 0.5 μ m . 6 Currents through K 1 channels of rat and human atrial myocytes were not inhibited by JKL1073A at concentrations up to 10 μ m . 7 These results indicate that JKL1073A exerts a positive inotropic effect by inhibition of I to . JKL1073A inhibit I to by binding to open state channels or shifting of the steady‐state inactivation curve of I to .