The local anesthetic butamben inhibits and accelerates low-voltage activated T-type currents in small sensory neurons.
Butamben (BAB) is a local anesthetic that can be used in epidural suspensions for long-term selective suppression of dorsal root pain signal transmission and in ointments for the treatment of skin pain. Previously, high-voltage activated N-type calcium channel inhibition has been implicated in the analgesic effect of BAB. In the present study we show that low-voltage activated or T-type calcium channels may also contribute to this effect. Typical transient T-type barium currents, selectively evoked by low-voltage (-40 mV) clamp stimulation of small (approximately 20 microm diameter) dorsal root ganglion neurons from newborn mice, were inhibited by BAB with an IC50 value of approximately 200 microM. Furthermore, 200 microM BAB accelerated T-type current activation, deactivation, and inactivation kinetics, comparable to earlier observations for N-type calcium channels. Finally, 200 microM BAB had no effect on the midpoint potential and slope factor of the activation curve, although it caused a approximately 3 mV hyperpolarizing shift of the inactivation curve, without affecting the slope factor. We conclude that BAB inhibits T-type calcium channels with a mechanism associated with channel kinetics acceleration.
Beekwilder
Jeroen P
JP
Department of Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
van Kempen
Gertrudis Th H
GT
van den Berg
Rutgeris J
RJ
Ypey
Dirk L
DL
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local; D000818:Animals; D000831:Animals, Newborn; D001566:Benzocaine / Q000031:analogs & derivatives*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; C004605:butamben; D001566:Benzocaine