Abstract
Papaverine, 1-[(3,4-dimethoxyphenyl)methyl]-6,-7-dimethoxyisoquinoline, has been used as a vasodilator agent and a therapeutic agent for cerebral vasospasm, renal colic, and penile impotence. We examined the effects of papaverine on a rapidly activating delayed rectifier K+channel (hKv1.5) cloned from human heart and stably expressed in Ltk− cells as well as a corresponding K+current (the ultrarapid delayed rectifier, IKur) in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, we found that papaverine inhibited hKv1.5 current in a time- and voltage-dependent manner with an IC50 value of 43.4 μM at +60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 μM) also blocked IKur in human atrial myocytes. These results indicate that papaverine blocks hKv1.5 channels and native hKv1.5 channels in a concentration-, voltage-, state-, and time-dependent manner. This interaction suggests that papaverine could alter cardiac excitability in vivo.
Footnotes
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This work was supported by Grant R05-2000-000-00199-0 from the Basic Research Program of the Korea Science and Engineering Foundation.
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DOI: 10.1124/jpet.102.042770
- Abbreviations:
- Kv channel
- voltage-gated K+channel
- IKur
- ultrarapid delayed rectifier
- I-V
- current-voltage
- IKr
- human ether-a-go-go-related gene-dependent K+ current
- Received August 4, 2002.
- Accepted October 3, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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