Effects of labedipinedilol-A, third-generation dihydropyridine-type calcium blocker, on ouabain-induced arrhythmia

Jhy Chong Liang, An Hsiang Huang, Jiunn Ren Wu, Shu Fen Liou, Zen Kong Dai, Ing Jun Chen, Jwu Lai Yeh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Labedipinedilol-A, a novel dihydropyridine-type calcium antagonist with α/β-adrenoceptor blocking properties, has been reported to produce a cardioprotective effect against ischemia reperfusion injury in rats. We investigated the protective effects of labedipinedilol-A on ouabain-induced tonotropy and arrhythmias in isolated whole atria, and using patch-clamp techniques to study the underlying mechanism of its antiarrhythmic activity on isolated cardiac myocytes. Labedipinedilol-A (10 μM) suppressed the tonotropic effect of ouabain significantly and prolonged the onset time of extra-systole (arrhythmia) induced by ouabain in isolate atria. In the voltage-clamp study, labedipinedilol-A (1-100 μM) reduced the peak amplitude of sodium inward current (INa) and L-type calcium current (I Ca-L), and shifted the current-voltage (I-V) curve upward in a concentration-dependent manner. In contrast, the addition of labedipinedilol-A increased transient outward potassium current (Ito) and inward rectifier potassium current (IK1) significantly. Labedipinedilol-A (10 μM) also effectively depressed the isoproterenol-induced increase in the Ca2+ current. These results show that labedipinedilol-A blocks I Ca-L and INa, and increases Ito and I K1. These findings indicate that labedipinedilol-A produces direct cardiac action, probably due to the inhibition of cardiac Na+ and Ca2+ channels. Our results suggest that labedipinedilol-A may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalDrug Development Research
Issue number1
Publication statusPublished - 2008 Feb
Externally publishedYes


  • Arrhythmia
  • Ca current
  • Calcium antagonist
  • K current
  • Na current
  • Ouabain
  • Ventricular myocyte

ASJC Scopus subject areas

  • Drug Discovery


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