An Experimental and Modeling Study of Na Current Heterogeneity in Rat Nodose Neurons and Its Impact on Neuronal Discharge. J.H. Schild and D.L. Kunze. Department of Physiology Pharmacology, Oregon Health Sciences University Portland, OR 97201, Rammelkamp Research Center, MetroHealth Medical Center 2500 MetroHealth Dr., Cleveland, OH 44109.
APStracts 4:219N, 1997.
ABSTRACT
This paper is a combined experimental and modeling study of two fundamental questions surrounding the functional characteristics of Na+ currents in nodose sensory neurons. First, when distinctly different classes of Na+ currents are expressed in the same neuron, is there a significant difference in the biological variability associated with 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 neurons using the patch-clamp technique. Two general populations of neurons were observed. A-type neurons (n = 20) expressed a single rapidly inactivating TTX-sensitive (TTX-S) Na+ current. C-type neurons (n = 87) co-expressed this TTX-S current along with a slowly inactivating 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 rates of activation but required potentials 20-30 mV more depolarized to reach threshold. Over the same clamp voltages the rates of inactivation for the TTX-R current were 3-9 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 msec as compared to 100-200 msec). Across the population of neurons studied the TTX-S data formed a relatively tight statistical distribution, exhibiting low standard deviations across all voltage- and time-dependent properties. In contrast, the same pooled measurements on the TTX-R data exhibited standard deviations that were 3-10 times larger. The statistical profiles of the voltage- and time-dependent properties of these currents were then used as a physiological guide to adjust the relevant parameters of a mathematical model of nodose sensory neurons previously developed by our group. 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 waveshapes of sensory neurons. We propose that the spectrum of variability exhibited by the TTX-R current in addition to its robust reactivation characteristics are important determinants in establishing the heterogeneous stimulus-response characteristics often observed across the general population of C-type sensory neurons. 

Received 19 May 1997; accepted in final form 26 August 1997.
APS Manuscript Number J416-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 5 September 1997