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 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 microM at +60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 microM) 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.
Choe
Han
H
Department of Physiology, Ulsan University College of Medicine, Seoul, South Korea.
Lee
Yu-Kyung
YK
Lee
Yong-Tae
YT
Choe
Huhn
H
Ko
Seong-Hoon
SH
Joo
Chan-Uhng
CU
Kim
Min-Ho
MH
Kim
Gong-Soo
GS
Eun
Jae-Soon
JS
Kim
Jong-Hyun
JH
Chae
Soo-Wan
SW
Kwak
Yong-Geun
YG
D000818:Animals; D002478:Cells, Cultured; D002675:Child, Preschool; D051668:Delayed Rectifier Potassium Channels; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007223:Infant; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated
D051668:Delayed Rectifier Potassium Channels; C496981:KCNA5 protein, human; C496982:Kcna5 protein, mouse; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D010208:Papaverine