1. K_v7/KCNQ Channels Are Functionally Expressed In Oligodendrocyte Progenitor Cells2. The Effect And Mechanism Of Pirt On The Current Of P2X₃Receptor

Background: KCNQ channels are widely expressed in neurons and they have multipleimportant functions, including control of excitability, spike afterpotentials, adaptation, andtheta resonance. Mutations in KCNQ genes have been demonstrated to associate withhuman neurological pathologies. However, little is known about whether KCNQ channelsare expressed in oligodendrocyte lineage cells (OLCs) and their functions in OLCs.Methods and Findings: In this study, we characterized KCNQ expression in OLCs byRT-PCR, immunostaining and electrophysiology. KCNQ2-5mRNAs were expressed in allthree developmental stages of cultured rat OLCs. KCNQ proteins were also detected inNG2+cells in primary cultures and cortex slices. Voltage-clamp recording revealed that theIMantagonist XE991significantly reduce KCNQ channel current (IK (Q)) in OPCs but not indifferentiated oligodendrocytes. In addition, inhibition of KCNQ channels promotes OPCsmotility in vitro.Conclusions: These findings showed that KCNQ channels were functionally expressed inOLCs and may play an important role in OPCs functioning in physiological or pathologicalconditions. The gene encoding the P2X₃protein subunit was originally cloned from dorsal rootganglion (DRG) sensory neurons. P2X receptors are widely distributed in the centralnervous system of adult animals, except P2X₃receptor. P2X₃receptor are predominantlylocalized on small-to medium diameter C-fiber andA sensory neurons within the dorsalroot, trigeminal, and nodose sensory ganglia, suggesting a role in nociceptive transmission.The molecular mechanisms underlying the regulation of P2X₃receptor remain, however,unclear.Pirt is expressed specifically in the peripheral nervous system (PNS), predominantlyin nociceptive neurons. The present study suggests that Pirt positively regulatesTRPV1channel via PIP2, and Pirt-/-mice have impaired behavioral responses to noxiousstimuli. The colocalization of Pirt and P2X₃receptor strongly suggests that Pirt might beinvolved in the regulation of P2X₃receptor in nociceptive transmission of tissue and nerveinjury.In our present study we found that (â… ) Pirt inhibited the current of P2X₃receptor by13amino-acid residues of the intracellular N-terminal;(â…¡) Pirt interacted with P2X₃receptor;(â…¢) Pirt did not inhibit the expression of P2X₃receptor on cell membrane.Thus, Pirt mightinteract with P2X₃receptor to regulate its functioning, and this could explain the inhibitionof P2X₃receptor current by Pirt.