A novel enhancing effect of clofilium on transient outward-type cloned cardiac K+ channel currents

T. Kobayashi, G. Mikala, A. Yatani

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

1 The antiarrythmic drug, clofilium, has been shown to black several types of K+ channel currents. To investigate the effects of clofilium on the transient outward K+ current (I(to)), a cloned I(to)-type cardiac K+ channel (RHK1) was expressed in Xenopus oocytes and the drug effects were examined on whole cell currents. 2 Extracellular application of clofilium slightly inhibited the current at +60 mV from a holding potential of -80 mV. However, it unexpectedly enhanced the current from a holding potential of -60 mV in a dose-dependent manner (219 ± 39% of control at 100 μM). 3 This enhancement is probably due to an increase in the ratio of channels in the resting state during steady depolarization, since clofilium shifted the inactivation curve in the depolarizing direction. 4 LY97119, a tertiary ammonium analogue of clofilium, did not exhibit this enhancing effect but only inhibited the current. 5 Clofilium may be useful for the study of channel inactivation because this type of phenomenon has not been reported for any other drug.

Original languageEnglish
Pages (from-to)1222-1226
Number of pages5
JournalBritish Journal of Pharmacology
Volume114
Issue number6
Publication statusPublished - 1995

Fingerprint

LY 97119
Pharmaceutical Preparations
Xenopus
Ammonium Compounds
Oocytes
clofilium
Direction compound

Keywords

  • Antiarrythmic drug
  • Clofilium
  • Inactivation
  • K channel
  • Transient outward

ASJC Scopus subject areas

  • Pharmacology

Cite this

A novel enhancing effect of clofilium on transient outward-type cloned cardiac K+ channel currents. / Kobayashi, T.; Mikala, G.; Yatani, A.

In: British Journal of Pharmacology, Vol. 114, No. 6, 1995, p. 1222-1226.

Research output: Contribution to journalArticle

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N2 - 1 The antiarrythmic drug, clofilium, has been shown to black several types of K+ channel currents. To investigate the effects of clofilium on the transient outward K+ current (I(to)), a cloned I(to)-type cardiac K+ channel (RHK1) was expressed in Xenopus oocytes and the drug effects were examined on whole cell currents. 2 Extracellular application of clofilium slightly inhibited the current at +60 mV from a holding potential of -80 mV. However, it unexpectedly enhanced the current from a holding potential of -60 mV in a dose-dependent manner (219 ± 39% of control at 100 μM). 3 This enhancement is probably due to an increase in the ratio of channels in the resting state during steady depolarization, since clofilium shifted the inactivation curve in the depolarizing direction. 4 LY97119, a tertiary ammonium analogue of clofilium, did not exhibit this enhancing effect but only inhibited the current. 5 Clofilium may be useful for the study of channel inactivation because this type of phenomenon has not been reported for any other drug.

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