Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine

Pharmacology. 2015;96(3-4):124-30. doi: 10.1159/000437231. Epub 2015 Jul 22.

Abstract

Background: Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures.

Methods: A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons.

Results: Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential.

Conclusion: Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / pharmacology*
  • Animals
  • Carbamates / pharmacology
  • Dose-Response Relationship, Drug
  • Ganglia, Spinal / drug effects
  • HEK293 Cells
  • Humans
  • KCNQ2 Potassium Channel / drug effects*
  • KCNQ3 Potassium Channel / drug effects*
  • Membrane Potentials / drug effects
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Phenylenediamines / pharmacology
  • Potassium Channel Blockers / pharmacology*
  • Procaine / analogs & derivatives*
  • Procaine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced

Substances

  • Anesthetics, Local
  • Carbamates
  • KCNQ2 Potassium Channel
  • KCNQ3 Potassium Channel
  • Phenylenediamines
  • Potassium Channel Blockers
  • ezogabine
  • Procaine
  • chloroprocaine