Effect of mibefradil on sodium and calcium currents

Peter R. Strege, Cheryl E. Bernard, Yijun Ou, Simon J. Gibbons, Gianrico Farrugia

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


Interstitial cells of Cajal (ICC) generate the electrical slow wave. The ionic conductances that contribute to the slow wave appear to vary among species. In humans, a tetrodotoxin-resistant Na+ current (Na v1.5) encoded by SCN5A contributes to the rising phase of the slow wave, whereas T-type Ca2+ currents have been reported from cultured mouse intestine ICC and also from canine colonic ICC. Mibefradil has a higher affinity for T-type over L-type Ca2+ channels, and the drug has been used in the gastrointestinal tract to identify T-type currents. However, the selectivity of mibefradil for T-type Ca2+ channels over ICC and smooth muscle Na+ channels has not been clearly demonstrated. The aim of this study was to determine the effect of mibefradil on T-type and L-type Ca2+ and Na+ currents. Whole cell currents were recorded from HEK-293 cells coexpressing green fluorescent protein with either the rat brain T-type Ca2+ channel α13.3b + β2, the human intestinal L-type Ca2+ channel subunits α1C + β2, or Nav1.5. Mibefradil significantly reduced expressed T-type Ca2+ current at concentrations a ≥0.1 μM (IC50 = 0.29 μM), L-type Ca2+ current at > 1 μM (IC50 = 2.7 μM), and Na+ current at ≥ 0.3 μM (IC50 = 0.98 μM). In conclusion, mibefradil inhibits the human intestinal tetrodotoxin-resistant Na+ channel at submicromolar concentrations. Caution must be used in the interpretation of the effects of mibefradil when several ion channel classes are coexpressed.

Original languageEnglish (US)
Pages (from-to)G249-G253
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number2 52-2
StatePublished - Aug 2005


  • Gastrointestinal tract
  • Ion channel
  • Patch clamp

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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