SLOW SODIUM CONDUCTANCES OF DORSAL-ROOT GANGLION NEURONS - INTRANEURONAL HOMOGENEITY AND INTERNEURONAL HETEROGENEITY

1. Voltage-dependent Na+ conductances were studied in small (18-25 mu m diam) adult rat dorsal root ganglion (DRG) neurons with the use of t he whole cell patch-clamp technique. Na+ currents were also recorded f rom larger (44-50 mu m diam) neurons and compared with those of the sm all neurons. 2. The predominant Na+ conductance in the small neurons w as selective over tetramethylammonium by at least 10-fold and was resi stant to 1 mu M external tetrodotoxin (TTX). Na+ conductances in many larger DRG neurons were kinetically faster and, in contrast, were bloc ked by 1 mu M TTX. 3. The Na+ conductance in the small neurons was kin etically 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 act ivation half-time was comprised of an initial delay. Inactivation half -times were voltage dependent and ranged from II ms at -20 mV to 2 ms at +50 mV. 4. Peak slow Na+ conductances were near maximal with condit ioning potentials negative to -120 mV and were significantly reduced o r eliminated with conditioning potentials positive to -40 mV. The slow Na+ conductance increased gradually with test potentials extending fr om -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 (curre nt availability), respectively. 5. Kinetics remained stable within a g iven neuron over the course of an experiment. However, considerable ki netic variation was exhibited from neuron to neuron, such that the hal f-times of activation and of inactivation spanned an order of magnitud e. In all small neurons studied there appeared to be a singular kineti c component of the current, based on sensitivity to the conditioning p otential, voltage dependence of activation, and inactivation halftime. 6. Unique closing properties were exhibited by Na+ channels of the sm all neurons. Hyperpolarization following a depolarization-induced full y 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 reve aled that the underlying channels accumulated into a volatile inactiva ted state over the course of the preceding depolarization. 7. Larger n eurons had a different repertoire of Na+ conductances, with either onl y a TTX-sensitive, kinetically fast type, or a combination of fast TTX -sensitive and slow currents. In larger neurons the kinetically separa ble fast current had a greater sensitivity to the conditioning potenti al, i.e., a left-shifted steady-state inactivation curve. 8. The diffe rent properties of the slow Na+ conductance in different neurons is li kely to reflect heterogeneity of the structure of the underlying chann el molecule. Although consistent with what others have found in equiva lent preparations, this heterogeneity is far broader in scope than wha t has so far been described. We suggest that biosynthetic constraints within a given small neuron maintain ion channel uniformity.