Slow sodium conductances of dorsal root ganglion neurons: intraneuronal homogeneity and interneuronal heterogeneity.
1. Voltage-dependent Na+ conductances were studied in small (18-25 microns diam) adult rat dorsal root ganglion (DRG) neurons with the use of the whole cell patch-clamp technique. Na+ currents were also recorded from larger (44-50 microns diam) neurons and compared with those of the small neurons. 2. The predominant Na+ conductance in the small neurons was selective over tetramethylammonium by at least 10-fold and was resistant to 1 microM external tetrodotoxin (TTX). Na+ conductances in many larger DRG neurons were kinetically faster and, in contrast, were blocked by 1 microM TTX. 3. The Na+ conductance in the small neurons was kinetically slow. Activation half-times were voltage dependent and ranged from 2 ms at -20 mV to 0.7 ms at +50 mV. Approximately 50% of the activation half-time was comprised of an initial delay. Inactivation half-times were voltage dependent and ranged from 11 ms at -20 mV to 2 ms at +50 mV. 4. Peak slow Na+ conductances were near maximal with conditioning potentials negative to -120 mV and were significantly reduced or eliminated with conditioning potentials positive to -40 mV. The slow Na+ conductance increased gradually with test potentials extending from -40 to +40 mV. In some cells the conductance could be saturated at +10 mV. Peak conductance/voltage relationships, although stable in a given neuron, revealed marked variability among neurons, spanning > 20- and 50-mV domains for steady-state activation and inactivation (current availability), respectively. 5. Kinetics remained stable within a given neuron over the course of an experiment. However, considerable kinetic variation was exhibited from neuron to neuron, such that the half-times of activation and of inactivation spanned an order of magnitude. In all small neurons studied there appeared to be a singular kinetic component of the current, based on sensitivity to the conditioning potential, voltage dependence of activation, and inactivation half-time. 6. Unique closing properties were exhibited by Na+ channels of the small neurons. Hyperpolarization following a depolarization-induced fully inactivated state resulted in tail currents that appeared to be the consequence of reactivation of the slow Na+ conductance. Tail currents recorded at various times during a fixed level of depolarization revealed that the underlying channels accumulated into a volatile inactivated state over the course of the preceding depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Rizzo
M A
MA
Department of Neurology, Yale University School of Medicine, New Haven 06510.
Kocsis
J D
JD
Waxman
S G
SG
D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002413:Cations, Divalent; D015222:Sodium Channels; D002586:Cesium; D013779:Tetrodotoxin