FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

Abstract

Na+ ,K + -ATPase (NKA) is required to generate the resting membrane potential in neurons. Nociceptive afferent neurons express not only the α and β subunits of NKA but also the γ subunit FXYD2. However, the neural function of FXYD2 is unknown. The present study shows that FXYD2 in nociceptive neurons is necessary for maintaining the mechanical allodynia induced by peripheral inflammation. FXYD2 interacted with α1NKA and negatively regulated the NKA activity, depolarizing the membrane potential of nociceptive neurons. Mechanical allodynia initiated in FXYD2-deficient mice was abolished 4 days after inflammation, whereas it persisted for at least 3 weeks in wild-type mice. Importantly, the FXYD2/α1NKA interaction gradually increased after inflammation and peaked on day 4 post inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission. Thus, the increased FXYD2 activity may be a fundamental mechanism underlying the persistent hypersensitivity to pain induced by inflammation. Keywords: FXYD2; Na

Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

“…Gene expression profiles of DRG tissue have been also analyzed by microarray and RNA-sequencing (RNA-seq) techniques [17,18]. Although these methods have helped to identify the expression of neuromodulators such as natriuretic peptide B (NPB) [19] and regulators of Na + , K + -ATPase (NKA), including the γ-subunit of NKA (FXYD domain-containing ion transport regulator 2, Fxyd2) [20][21][22], they cannot provide a global view of the transcriptional profiles of individual neurons.…”

Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue

“…This would also validate that the antibody beads were binding intact exosomes. The transmembrane protein ion channel regulator FXYD2 isoforms γa and γb is reported to be an islet β cell-specific surface marker compared with exocrine pancreas (19)(20)(21)(22). Therefore, we assessed for FXYD2 surface coexpression Figure 4B).…”

Profile of Dr. Xu Zhang

“…These findings provide FSTL1 as a first endogenous NKA agonist that regulates synaptic transmission. Furthermore, they also revealed that the FXYD2/α1NKA interaction increased after inflammation, resulting in reduction of NKA activity, depolarization of neuron membrane and facilitation of excitatory afferent neurotransmission (Wang et al, 2015), revealing a fundamental mechanism underlying the persistent inflammatory pain.…”