The RNA Binding Complex Translin‐Trax Mediates Pro‐Excitatory Activity in Neurons

Abstract

In animal models of neurogenic hypertension the Rostral Ventrolateral Medulla (RVLM), of the brain, displays increased excitatory activity that is linked to elevated sympathetic tone and blood pressure. Analysis of gene expression in the RVLM of normotensive Wistar Kyoto (WKY) and Spontaneous Hypertensive Rat (SHR) revealed reduction of the protein Translin (TSN) in SHR. TSN and its partner Trax (TRX) form a complex that is thought to mediate dendritic trafficking of mRNA. To examine the functional effect of this complex, we dialyzed purified TSN‐TRX into cultured brain neurons from either WKY or SHR and measured its effect on the rate of action potential firing (APF). Basal APF rate was 1.4 Hz in WKY neurons and after 20 min control treated neurons showed a similar rate of 1.3 Hz. In contrast, TSN‐TRX treatment mediated a significant increase in APF rate to 1.9 Hz. Tsn alone had no effect in WKY neurons and SHR neurons showed no response to TSN‐TRX. Pretreatment with the RNA translation inhibitor, cycloheximide, abolished the excitatory effect of Tsn‐TRX in WKY neurons. Our results suggest that the excitatory effect of TSN‐TRX in WKY neurons is translation‐dependent. We hypothesize that homeostatic feedback mechanisms in SHR neurons lead to downregulation of TSN levels and the resistance of these cells to the excitatory effects of the TSN‐TRX complex. This work was supported by funding from NHLBI, NIDA of the NIH and NARSAD.