GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9
作者： Johan A. R. Östman , Mohammed A. Nassar , John N. Wood , Mark D. Baker
DOI: 10.1113/JPHYSIOL.2007.147942
关键词: GTP' 、 Nociception 、 Cell biology 、 Chemistry 、 Sensory system 、 Nociceptor 、 Frameshift mutation 、 Nav1.9 、 Internal medicine 、 Intracellular 、 Endocrinology 、 Sodium channel
摘要: Persistent tetrodotoxin-resistant (TTX-r) sodium currents up-regulated by intracellular GTP have been invoked as the site of action peripheral inflammatory mediators that lower pain thresholds, and ascribed to NaV1.9 channel. Here we describe properties a global knock-out produced replacing exons 4 5 in SCN11A with neomycin resistance cassette, deleting domain 1 voltage sensor introducing frameshift mutation. Recordings from small (< 25 μm apparent diameter) sensory neurones indicated channel loss eliminates TTX-r persistent current. Intracellular dialysis GTP-γ-S did not cause an up-regulation Na+ current NaV1.9-null concomitant negative shift voltage-threshold seen wild-type heterozygous neurones. Heterologous hNaV1.9 expression confirms human clone can restore Taken together, these findings demonstrate underlies G-protein pathway-regulated diameter may drive spontaneous discharge nociceptive nerve fibres during inflammation.
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