Abstract 474: Impaired Excitability of Renal Afferent Innervation in an in-vitro Model of Inflammation.

Abstract

INTRODUCTION AND AIMS: Renal denervation may be beneficial in hypertension with inflammatory renal disease: in hypertension renal afferent control of sympathetic nerve activity could be impaired. Recently, we found that afferent renal neurons showed a characteristic excitability, exhibiting predominantly a sustained firing upon current injection. So far, excitability of these neurons under pathological conditions such as renal inflammation in hypertension is unclear. Hence, in an in vitro model we wanted to test the hypothesis that a proinflammatory mediator like CXCL1 could alter the firing pattern of neurons with renal afferents and thus decrease their excitability. METHODS: Dorsal root ganglion (DRG) neurons (Th11-L2) were incubated with the chemokine CXCL1 (1,5nmol/ml) for 12 hours before patch clamp recordings. Labelling (DiI) allowed the identification of renal afferent neurons. Current clamp was used to characterize neurons as “tonic”, i.e. sustained action potential (AP) firing or “phasic”, i.e. <5 APs according to their firing response to current injections. AP properties were determined in renal and non-renal neurons incubated with CXCL1 and compared to controls. Results: Renal afferent DRG neurons exhibited in 57% (23 of 41) a tonic firing pattern vs.11,7% (3 of 27)* in non-renal neurons. However, exposed to the chemokine, renal DRG neurons exhibited significantly to a lesser degree tonic firing (35,6% [35 of 101] vs. 57% [23 of 41], *p<0,05) but instead an increased occurrence of phasic firing. Renal DRG neurons with phasic firing pattern showed a significantly lower threshold for AP-firing (600pA [320-1000] vs.1000pA [400-3200]) and a significantly shorter AP-duration at threshold-level (2,095ms [1,75-4,25] vs. 5,15ms [4,3- 8,7]) after exposure to CXCL1. Conclusion: We could show that after exposure to a proinflammatory mediator like CXCL1, renal afferent DRG neurons exhibited a significantly higher proportion of neurons with a phasic pattern (<5 APs) and decreased excitability as compared to control conditions. Significant changes in action potential properties of phasic neurons point to an altered sodium channel expression likely inducing a faster inactivation of these channels with decreased firing activity.