EXPERIMENTAL AND MODELING STUDY OF NA+ CURRENT HETEROGENEITY IN RAT NODOSE NEURONS AND ITS IMPACT ON NEURONAL DISCHARGE

This paper is a combined experimental and modeling study of two fundam ental questions surrounding the functional characteristics of Na+ curr ents in nodose sensory neurons. First, when distinctly different class es of Na+ currents are expressed in the same neuron, is there a signif icant difference in the intrinsic biological variability associated wi th the voltage-and time-dependent properties of these currents? Second , in what manner can such variability in functional properties impact the discharge characteristics of these neurons? Here, we recorded the whole cell Na+ currents in acutely dissociated rat nodose sensory neur ons using the patch-clamp technique. Two general populations of neuron s were observed. A-type neurons (n = 20) expressed a single rapidly in activating tetrodotoxin-sensitive (TTX-R) Na+ current. C-type neurons (n = 87) coexpressed this TTX-S current along with a slowly inactivati ng TTX-resistant (TTX-R) Na+ current. The TTX-S currents in both cell types had submillisecond rates of activation at room temperature with thresholds near -50 mV. The TTX-R current exhibited about the same rat es of activation but required potentials 20-30 mV more depolarized to reach threshold. Over the same clamp voltages the rates of inactivatio n for the TTX-R current were three to nine times slower than those for the TTX-S current. However, the TTX-R current recovered from complete inactivation at a rate 10-20 times faster than the TTX-S current (10 ms as compared with 100-200 ms). Across the population of neurons stud ied the TTX-S data formed a relatively tight statistical distribution, exhibiting low standard deviations across all measured voltage-and ti me-dependent properties. In contrast, the same pooled measurements on the TTX-R data exhibited standard deviations that were 3-10 times larg er. The statistical profiles of the voltage-and time-dependent propert ies of these currents then were used as a physiological guide to adjus t the relevant parameters of a mathematical model of nodose sensory ne urons previously developed by our group (Schild et al. 1994). Here, we show how the relative expression of TTX-S and TTX-R Na+ currents and the differences in their apparent biological variability can shape the regenerative discharge characteristics and action potential waveshape s of sensory neurons. We propose that the spectrum of variability robu st reactivation characteristics of the TTX-R current are important det erminants in establishing the heterogeneous stimulus-response characte ristics often observed across the general population of C-type sensory neurons.