Papaverine Blocks hKv1.5 Channel Current and Human Atrial Ultrarapid Delayed Rectifier K+ Currents

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...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2003-02, Vol.304 (2), p.706-712
Main Authors: Choe, Han, Lee, Yu-Kyung, Lee, Yong-Tae, Choe, Huhn, Ko, Seong-Hoon, Joo, Chan-Uhng, Kim, Min-Ho, Kim, Gong-Soo, Eun, Jae-Soon, Kim, Jong-Hyun, Chae, Soo-Wan, Kwak, Yong-Geun
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Child, Preschool
Delayed Rectifier Potassium Channels
Heart Atria - cytology
Heart Atria - drug effects
Humans
Infant
Kv1.5 Potassium Channel
Membrane Potentials - drug effects
Membrane Potentials - physiology
Mice
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - physiology
Papaverine - pharmacology
Potassium Channel Blockers - pharmacology
Potassium Channels - physiology
Potassium Channels, Voltage-Gated
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Summary: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, I Kur ) 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 IC 50 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 I Kur 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.
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.102.042770