Comparative effects of ultra-short-acting beta1-blockers on voltage-gated tetrodotoxin-resistant Na+ channels in rat sensory neurons

Eur J Anaesthesiol. 2009 Mar;26(3):196-200. doi: 10.1097/EJA.0b013e32831ac268.


Background and objective: To examine a possible mechanism for their antinociceptive actions, we compared the effects of two clinically used ultra-short-acting beta1-blockers, landiolol and esmolol, on tetrodotoxin-resistant sodium (TTX-r Na) channels in rat dorsal root ganglion neurons, which are important for nociception.

Methods: In small (<30 microm) dorsal root ganglion neurons from Sprague-Dawley rats, recordings of whole-cell membrane currents were made using the patch-clamp technique. To examine the effects of landiolol and esmolol on TTX-r Na currents, whole-cell membrane Na currents were evoked every 10 s by stepping for 50 ms from a holding potential of -70 to -10 mV. Each drug was applied at stepwise-increased concentrations every 2 min. The voltage dependence of the steady-state inactivation of the TTX-r Na current was investigated by using a conventional double-pulse protocol. To test for use-dependent blockade of TTX-r Na channels by beta-blockers, trains of depolarizing pulses (to -10 from a holding potential of -70 mV) were applied at one of three frequencies (0.2, 5 or 20 Hz) in the absence or presence of drug (landiolol 8 mmol l, esmolol 140 micromol l).

Results: Esmolol blocked TTX-r Na currents in a dose-dependent and use-dependent manner, but a very high concentration of landiolol was required to block TTX-r Na channel activities. The half-maximal inhibitory concentrations (IC50) for the TTX-r Na current were (holding potential, -70 mV) landiolol 7.66 +/- 0.62 mmol l (n = 6) and esmolol 145 +/- 7.5 micromol l (n = 6), and the Hill coefficients were landiolol 1.06 +/- 0.09 (n = 6) and esmolol 0.96 +/- 0.05 (n = 6).

Conclusion: Esmolol, but not landiolol, may have useful effects against pain related to TTX-r Na channel activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Drug Resistance / drug effects*
  • Electrophysiological Phenomena
  • Ion Channel Gating / drug effects*
  • Kinetics
  • Male
  • Morpholines / pharmacology
  • Patch-Clamp Techniques
  • Propanolamines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / metabolism*
  • Sodium Channels / metabolism*
  • Tetrodotoxin / pharmacology*
  • Time Factors
  • Urea / analogs & derivatives
  • Urea / pharmacology


  • Adrenergic beta-Antagonists
  • Morpholines
  • Propanolamines
  • Sodium Channels
  • Tetrodotoxin
  • landiolol
  • Urea
  • esmolol