Mibefradil (Ro 40-5967) blocks multiple types of voltage-gated calcium channels in cultured rat spinal motoneurones

Cell Calcium. 1997 Oct;22(4):299-311. doi: 10.1016/s0143-4160(97)90068-3.


The actions of the novel calcium (Ca2+) channel antagonist mibefradil (Ro 40-5967), a selective T-type channel blocker in myocardium, were investigated in embryonic rat spinal motoneurones maintained in culture. Whole-cell currents were recorded with the patch-clamp technique. Motoneurones displayed transient, low-voltage-activated (LVA) and, more sustained, high-voltage-activated (HVA) Ca2+ currents. The LVA currents were small and preferentially blocked by amiloride and low doses of nickel. Most of the HVA Ca2+ current flowed through N-type Ca2+ channels, while L-, and P/Q-type channels represented a smaller fraction. Mibefradil caused a rapid and reversible dose-dependent block of inward Ca2+ channel currents. Inhibition was nearly complete at 10 microM, suggesting mibefradil blockade of all subclasses of Ca2+ channels. The IC50 was approximately 1.4 microM on currents measured at 0 mV, from a holding potential of -90 mV. Inhibition of LVA Ca2+ current occurred over the same contraction range. Slow tail currents induced by the dihydropyridine agonist Bay K 8644 were also blocked by mibefradil, although with a slightly lower potency (IC50 = 3.4 microM). These broad inhibitory effects of mibefradil on Ca2+ influx were also supported by the strong inhibition of depolarization-induced intracellular calcium transients, measured from Indo-1 loaded motoneurones imaged with confocal microscopy. We conclude that mibefradil has potent blocking effects on Ca2+ channels in mammalian motoneurones. We hypothesize that therapeutic and pharmacological effects of mibefradil may involve actions on Ca2+ channels other than type T.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Cells, Cultured
  • Electric Conductivity
  • Electrophysiology
  • Female
  • Ion Channel Gating / drug effects*
  • Mibefradil
  • Motor Neurons / cytology
  • Motor Neurons / drug effects
  • Motor Neurons / metabolism*
  • Rats
  • Spine / cytology
  • Spine / embryology
  • Tetrahydronaphthalenes / pharmacology*


  • Benzimidazoles
  • Calcium Channel Blockers
  • Calcium Channels
  • Tetrahydronaphthalenes
  • Mibefradil