A Sodium Leak Current Regulates Pacemaker Activity of Adult Central Pattern Generator Neurons in Lymnaea Stagnalis

Tom Z. Lu,Zhong-Ping Feng,Vladimir Brezina

doi:10.1371/journal.pone.0018745

Abstract

The resting membrane potential of the pacemaker neurons is one of the essential mechanisms underlying rhythm generation. In this study, we described the biophysical properties of an uncharacterized channel (U-type channel) and investigated the role of the channel in the rhythmic activity of a respiratory pacemaker neuron and the respiratory behaviour in adult freshwater snail Lymnaea stagnalis. Our results show that the channel conducts an inward leak current carried by Na+ (ILeak-Na). The ILeak-Na contributed to the resting membrane potential and was required for maintaining rhythmic action potential bursting activity of the identified pacemaker RPeD1 neurons. Partial knockdown of the U-type channel suppressed the aerial respiratory behaviour of the adult snail in vivo. These findings identified the Na+ leak conductance via the U-type channel, likely a NALCN-like channel, as one of the fundamental mechanisms regulating rhythm activity of pacemaker neurons and respiratory behaviour in adult animals.

Highlights

The rhythmic activities of the central pattern generator neurons (CPG) are essential for numerous biological functions, including brain development [1,2], locomotion [3], energy balance [4], and respiration [5,6]
We investigated the biophysical properties and involvement of the U-type channel in the rhythmic activity of the rCPG pacemaker right pedal dorsal 1 (RPeD1) neuron, and in the aerial respiratory behaviour of the snail, using an RNAi gene silencing approach combined with electrophysiological recordings
We have demonstrated that an inward Na+conductance leak current component at rest regulates the rhythmic activity of a respiratory pacemaker neuron, RPeD1

Summary

Introduction

The rhythmic activities of the central pattern generator neurons (CPG) are essential for numerous biological functions, including brain development [1,2], locomotion [3], energy balance [4], and respiration [5,6]. The true CPG pacemaker neurons are capable of generating intrinsic bursting rhythms in dependent of synaptic input. One conserved mechanism that is a prerequisite for spontaneous rhythmic activity of pacemaker neurons is regulation of the resting membrane potential (RMP). K+ leak has been the classical mechanism to describe regulation of the RMP [7]; the highly depolarized membrane potential of many pacemaker neurons suggests additional current components [4,5,8,9]. The aerial respiration of L. stagnalis is controlled by a simple well-described rCPG network consisting of three large identified neurons [13], including one intrinsic pacemaker neuron, the right pedal dorsal 1 (RPeD1), that initiates rCPG rhythmic activity [13,14]. L. stagnalis has been used as an animal model to study rCPG properties and regulation [10,15,16]

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Conclusion