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 (∼20 μm diameter) dorsal root ganglion neurons from newborn mice, were inhibited by BAB with an IC50 value of ∼200 μM. Furthermore, 200 μM BAB accelerated T-type current activation, deactivation, and inactivation kinetics, comparable to earlier observations for N-type calcium channels. Finally, 200 μM BAB had no effect on the midpoint potential and slope factor of the activation curve, although it caused a ∼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.