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MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability
Journal article   Open access   Peer reviewed

MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability

Robert A Crozier, Seena K Ajit, Edward J Kaftan and Mark H Pausch
The Journal of neuroscience, v 27(16), pp 4492-4496
18 Apr 2007
DOI: https://doi.org/10.1523/JNEUROSCI.4932-06.2007
PMID: 17442834
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
http://www.jneurosci.org/content/27/16/4492.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1523/JNEUROSCI.4932-06.2007View
Published, Version of Record (VoR) Open

Abstract

Action Potentials - physiology Animals CHO Cells Cricetinae Cricetulus Ganglia, Spinal - metabolism KCNQ2 Potassium Channel - metabolism KCNQ3 Potassium Channel - metabolism Male Neurons - physiology Patch-Clamp Techniques Rats Rats, Long-Evans Rats, Sprague-Dawley Receptors, G-Protein-Coupled - metabolism
The recently identified Mas-related gene (Mrg) family of G-protein-coupled receptors is expressed almost exclusively in dorsal root ganglion (DRG) neurons. The expression of one family member, MrgD, is even further confined to IB4+, nonpeptidergic, small-diameter nociceptors. Although the functional consequences of MrgD activation are not known, this expression profile provides intriguing potential for a role in pain sensation or modulation. In a recombinant cell line, we first assessed the functional significance of MrgD activation by coexpressing MrgD with the KCNQ2/3 potassium channel, a channel implicated in pain. Whole-cell voltage-clamp recordings revealed that bath application of the ligand for MrgD, beta-alanine, resulted in robust inhibition of KCNQ2/3 activity. Pharmacological blockade of G(i/o) and phospholipase C signaling revealed a partial and complete block of the response, respectively. We extended these observations to dissociated DRG neuron cultures by examining MrgD modulation of M-currents (carried primarily by KCNQ2/3). Here too, beta-alanine-induced activation of endogenous MrgD inhibited M-currents, but primarily via a pertussis toxin-sensitive pathway. Finally, we assessed the consequence of beta-alanine-induced activation of MrgD in phasic neurons. Phasic neurons that fired a single action potential (AP) before beta-alanine application fired multiple APs during beta-alanine exposure. In sum, we provide evidence for a novel interaction between MrgD and KCNQ/M-type potassium channels that contributes to an increase in excitability of DRG neurons and thus may enhance the signaling of primary afferent nociceptive neurons.

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