Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons

Pedro L. Martinez-Espinosa, Jianping Wu, Chengtao Yang, Vivian Gonzalez-Perez, Huifang Zhou, Hongwu Liang, Xiao Ming Xia, Christopher J. Lingle

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.

Original languageEnglish
Article numbere10013
JournaleLife
Volume4
Issue numberNOVEMBER2015
DOIs
StatePublished - Nov 11 2015

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