TY - JOUR
T1 - Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons
AU - Martinez-Espinosa, Pedro L.
AU - Wu, Jianping
AU - Yang, Chengtao
AU - Gonzalez-Perez, Vivian
AU - Zhou, Huifang
AU - Liang, Hongwu
AU - Xia, Xiao Ming
AU - Lingle, Christopher J.
N1 - Publisher Copyright:
© Martinez-Espinosa et al.
PY - 2015/11/11
Y1 - 2015/11/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84949968524&partnerID=8YFLogxK
U2 - 10.7554/eLife.10013
DO - 10.7554/eLife.10013
M3 - Article
C2 - 26559620
AN - SCOPUS:84949968524
SN - 2050-084X
VL - 4
JO - eLife
JF - eLife
IS - NOVEMBER2015
M1 - e10013
ER -