Comparison of the electrophysiological effects of S49, CSH087 and CSH068 in rat ventricular cells
Chen, L.; Lee, C.S.; Su, M.J.
Proceedings of the National Science Council Republic of China. Part B Life Sciences 17(2): 48-56
1993
ISSN/ISBN: 0255-6596 PMID: 7528932 Document Number: 407307
S49, CSH087 and CSH068 are aporphine alkaloids and are synthesized from vanillin. In the present study, the effects of these compounds on the action potential and membrane currents of rat ventricular cells were examined by using the whole cell recording technique with single suction pipettes. At a stimulation frequency of 0.1 Hz, S49 (1.5 mu-M), CSH087 (3 mu-M) and CSH068 (3 mu-M) could prolong the action potential durations (APD-50 and APD-90). Voltage clamp studies revealed inhibition of the transient outward currents by S49, CSH087 and CSH068 with K-D of 2.0, 1.8 and 5.2 mu-M, respectively, but a lack of enhancement of calcium influx. Therefore, the inhibition of the potassium conductance may explain the prolongation of APD induced by these compounds. In contrast, the late potassium outward current was more resistant to CSH087 and S49, but was blocked by CSH068 with a K-D of 6.4 mu-M. The sodium inward current (I-Na) also was inhibited by S49, CSH087 and CSH068 in a dose-dependent manner with K-D of 1.2, 6.8 and 7.5 mu-M, respectively (at a holding potential of -80 mV). The inhibition of I-Na was enhanced at a less negative holding potential. The voltage-dependent inhibition Of I-Na was associated with the shift of the I-Na availability curve to more negative potentials. These results indicate that these compounds have high affinity for inactivated Na+ channels. A twin-pulse experiment revealed that these compounds increased the recovery time constant of I-Na. The potency for the shift of the I-Na availability curve and the retardation of I-Na recovery from inactivation were S49 gt CSH087 and CSH068. The present findings suggest that S49, CSH087 and CSH068 may act as class I and class III antiarrhythmic agents.