Comparison of the inhibitory effects of PDE inhibitors on the HERG current

It has been reported that some phosphodiesterase (PDE) inhibitors prolong cardiac action potential duration by inhibiting the delayed rectifier K+ current, IK. However, comparative studies on the inhibitory effects of PDE inhibitors on IK are few. In this study, we examined the effects of PDE inhibi...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2004, Vol.94 (suppl.2), p.158-158
Main Authors: Kiyokazu Yunomae, Qi Gong, Satoko Ichisaki, Junko Matuo, Shin-ichi Nagayama, Rhoichi Nagata, Go Kito
Format: Article
Language:Japanese
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Summary:It has been reported that some phosphodiesterase (PDE) inhibitors prolong cardiac action potential duration by inhibiting the delayed rectifier K+ current, IK. However, comparative studies on the inhibitory effects of PDE inhibitors on IK are few. In this study, we examined the effects of PDE inhibitors on HERG current in CHO-K1 cells using the whole-cell patch-clamp technique, and compared the effects of PDE inhibitors at room temperature. The PDE inhibitors, vinpocetine (VP), EHNA, vesnarinone (VN), rolipram and dipyridamole, inhibited HERG currents. VP and VN significantly inhibited HERG currents and induced concentration-dependent inhibition (IC50; 16.4 and 0.83μM, respectively). The effects of VP and VN were not significantly affected by the co-application of protein kinase (PK) inhibitors (H-89 and staurosporine, a specific PKA inhibitor and a nonspecific PK inhibitor, respectively). These results showed that the HERG inhibitory effects of VP and VN were stronger than those of any other PDE inhibitor, but that their PDE inhibitory effects might not be involved in the inhibition of HERG currents.
ISSN:1347-8613