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Anesth Analg 2006;102:141-145
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000189599.79451.34

ANESTHETIC PHARMACOLOGY

The Local Anesthetic Butamben Inhibits and Accelerates Low-Voltage Activated T-Type Currents in Small Sensory Neurons

Jeroen P. Beekwilder, MSc, Gertrudis Th.H. van Kempen, BSc, Rutgeris J. van den Berg, PhD, and Dirk L. Ypey, PhD

Department of Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands

Address correspondence to D. L. Ypey, PhD, Department of Neurophysiology, Leiden University Medical Center, PO Box 9604, 2300 RC Leiden, The Netherlands. Address e-mail to D.L.Ypey{at}lumc.nl.

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.




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L. J.A. Rampaart, J. P. Beekwilder, G. Th.H. van Kempen, R. J. van den Berg, and D. L. Ypey
The Local Anesthetic Butamben Inhibits Total and L-Type Barium Currents in PC12 Cells
Anesth. Analg., June 1, 2008; 106(6): 1778 - 1783.
[Abstract] [Full Text] [PDF]


Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.