The block of total and N-type calcium conductance in mouse sensory neurons by the local anesthetic n-butyl-p-aminobenzoate.
To contribute to the understanding of the mechanism underlying selective analgesia by epidural application of suspensions of the local anesthetic butamben (n-butyl-p-aminobenzoate; BAB), we investigated the effect of dissolved BAB on calcium channels in sensory neurons. Small-diameter dorsal root ganglion neurons from newborn mice were used to measure whole-cell barium or calcium currents through calcium channels upon voltage-clamp stimulation. BAB suppressed the voltage-step-evoked barium current of these cells in a concentration-dependent manner with a 50% inhibitory concentration of 207 +/- 14 microM (n = 40). A similar concentration dependency was found for the pharmacologically isolated N-type component of the whole-cell barium current. The time constants of inactivation and deactivation of the N-type current became smaller in the presence of BAB, thus suggesting that kinetic changes are involved in the inhibition of this current. BAB caused a similar inhibition of the total calcium current and its N-type component when these currents were evoked by command potentials with the shape of an action potential. This inhibition of calcium currents by BAB should be considered in the search for the mechanism of selective analgesia by epidural suspensions of this local anesthetic.
Beekwilder
Jeroen P
JP
Department of Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
Winkelman
Daniel L B
DLB
van Kempen
Gertrudis Th H
GTH
van den Berg
Rutgeris J
RJ
Ypey
Dirk L
DL
D000200:Action Potentials / Q000187:drug effects; D000465:Algorithms; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001464:Barium; D001566:Benzocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D001464:Barium; C004605:butamben; D001566:Benzocaine