Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception.

Nana Song,Qijun Du,Qian Jiang,Comron J Hassanzadeh,Linlin Shen,Ruijuan Guan,Xiaomei Zhao,Yuyang Chu,Xiang-Ping Chu,Xia Wang,Dawei Yang

doi:10.1038/srep38777

Abstract

The role of acid-sensing ion channels (ASICs) in the ventrolateral medulla (VLM) remains uncertain. Here, we found that ASIC1a and ASIC2 are widely expressed in rat medulla, and the expression level is higher at neonatal stage as compared to adult stage. The two ASIC subunits co-localized in medualla neurons. Furthermore, pH reduction triggered typical ASIC-type currents in the medulla, including the VLM. These currents showed a pH50 value of 6.6 and were blocked by amiloride. Based on their sensitivity to psalmotoxin 1 (PcTx1) and zinc, homomeric ASIC1a and heteromeric ASIC1a/2 channels were likely responsible for acid-mediated currents in the mouse medulla. ASIC currents triggered by pH 5 disappeared in the VLM neurons from ASIC1−/−, but not ASIC2−/− mice. Activation of ASICs in the medulla also triggered neuronal excitation. Moreover, microinjection of artificial cerebrospinal fluid at a pH of 6.5 into the VLM increased integrated phrenic nerve discharge, inspiratory time and respiratory drive in rats. Both amiloride and PcTx1 inhibited the acid-induced stimulating effect on respiration. Collectively, our data suggest that ASICs are highly expressed in the medulla including the VLM, and activation of ASICs in the VLM contributes to central chemoreception.

Highlights

Reported in the hypothalamus[34], but its level is much lower compared to ASIC1a and ASIC235,36
Protein levels of ASIC1 and ASIC2a in the ventrolateral medulla (VLM) were decreased in the adults as compared to neonatal rats
Our data suggests that ASIC1 and ASIC2a are expressed in the medulla of the rat including the VLM and protein levels of both rat ASIC1 and ASIC2a are decreased in the adults as compared to neonatal rats

Summary

Introduction

Reported in the hypothalamus[34], but its level is much lower compared to ASIC1a and ASIC235,36. Previous studies have shown that ASICs in the lateral hypothalamus and the nucleus of the solitary tract (NTS) contribute to central regulation of respiration[37,38]. Little is known about the expression and functional role of ASICs in the VLM. We hypothesize that ASICs are expressed in the VLM, and they contribute to central chemoreception. To test this hypothesis, we studied ASIC expression in the rat medulla and acid-activated currents in the mouse medulla. To address the functional effect of ASIC activation, we performed in vivo microinjection of acidic artificial cerebrospinal fluid (ACSF) in rats. Our data revealed an important role of ASICs in regulating central chemoreception in the medulla

Methods

Results

Conclusion