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Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge.
J H Schild, D L Kunze
J. Neurophysiol.,
1997
Dec
, 78, 3198209
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 intrinsic biological variability associated with the voltage and timedependent 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 patchclamp technique. Two general populations of neurons were observed. Atype neurons (n = 20) expressed a single rapidly inactivating tetrodotoxinsensitive (TTXS) Na+ current. Ctype neurons (n = 87) coexpressed this TTXS current along with a slowly inactivating TTXresistant (TTXR) Na+ current. The TTXS currents in both cell types had submillisecond rates of activation at room temperature with thresholds near 50 mV. The TTXR current exhibited about the same rates of activation but required potentials 2030 mV more depolarized to reach threshold. Over the same clamp voltages the rates of inactivation for the TTXR current were three to nine times slower than those for the TTXS current. However, the TTXR current recovered from complete inactivation at a rate 1020 times faster than the TTXS current (10 ms as compared with 100200 ms). Across the population of neurons studied the TTXS data formed a relatively tight statistical distribution, exhibiting low standard deviations across all measured voltage and timedependent properties. In contrast, the same pooled measurements on the TTXR data exhibited standard deviations that were 310 times larger. The statistical profiles of the voltage and timedependent properties of these currents then were 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 TTXS and TTXR 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 robust reactivation characteristics of the TTXR current are important determinants in establishing the heterogeneous stimulusresponse characteristics often observed across the general population of Ctype sensory neurons.
http://www.ncbi.nlm.nih.gov/pubmed/9405539
