The local anesthetic, n-butyl-p-aminobenzoate, reduces rat sensory neuron excitability by differential actions on fast and slow Na+ current components.
Effects of the local anesthetic, n-butyl-p-aminobenzoate, at a concentration of 100 microM, were investigated using the whole-cell voltage clamp on dorsal root ganglion neurons cultured from neonatal rat in a serum-enriched medium. During current clamp conditions, the drug either increased the firing threshold or blocked tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ action potentials. These actions were reversible. Under voltage clamp conditions, inactivation of the Na+ current revealed the existence of 3 fast Na+ current components, termed F1, F2 and F3 (tetrodotoxin-sensitive) and 2 slow ones, termed S1 and S2 (tetrodotoxin-resistant). The local anesthetic shifted the midpoint potentials of Na+ inactivation curves for F1, F2 and F3 currents by 7, 21 and 6 mV, respectively, towards hyperpolarizing membrane voltages whereas it did not influence these potentials for the slow currents. The amplitudes of only F3 and S2 currents were reduced by n-butyl-p-aminobenzoate to 24 and 11%, respectively, of their control values. These results show that the local anesthetic has a differential mode of action on the 5 types of Na+ currents, which are apparently present in cultured sensory neurons. This differential action can play an important role in the selective analgesic effect observed after epidural administration of a 10% n-butyl-p-amino-benzoate suspension.
Van den Berg
R J
RJ
Department of Physiology and Physiological Physics, University of Leiden, The Netherlands.
Wang
Z
Z
Grouls
R J
RJ
Korsten
H H
HH
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012680:Sensitivity and Specificity; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology*; D012996:Solutions; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D015222:Sodium Channels; D012996:Solutions; D013779:Tetrodotoxin; D012964:Sodium; C004605:butamben; D001566:Benzocaine