Differential properties of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root ganglion neurons.
TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) sodium channel currents were analyzed in acutely dissociated dorsal root ganglion (DRG) neurons isolated from 3-12-d-old and adult rats. Currents were recorded using the whole-cell patch-clamp technique. TTX-R current was more likely to be present in younger animals (3-7 d), whereas TTX-S current was more common in older animals (7-10 d), although TTX-R current was recorded from adult rat DRG neurons. The TTX-R and TTX-S currents differed in their steady-state inactivation, with 50% inactivation voltage at -40 +/- 5 mV (n = 10) for TTX-R currents and -70 +/- 4 mV (n = 10) for TTX-S currents. These current types also differed in their activation kinetics, with 50% activation values of -15 +/- 5 mV (n = 5) for TTX-R currents and -26 +/- 6 mV (n = 5) for TTX-S currents. The interactions of TTX-R and TTX-S channels with various pharmacological agents and divalent cations were studied. The Kd values for TTX-S and TTX-R currents were estimated to be 0.3 nM and 100 microM for TTX, 0.5 nM and 10 microM for saxitoxin, and 50 microM and 200 microM for lidocaine, respectively. TTX-S channels did not exhibit a marked use-dependent block by lidocaine, whereas lidocaine significantly decreased TTX-R current in a use-dependent manner at frequencies ranging from 1 to 33.3 Hz. Several external divalent cations exerted different effects on these current types.(ABSTRACT TRUNCATED AT 250 WORDS)
Roy
M L
ML
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Narahashi
T
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D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006706:Homeostasis; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D012530:Saxitoxin / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology*
D002413:Cations, Divalent; D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin; D008012:Lidocaine