Knockdown of zebrafish Nav1.6 sodium channel impairs embryonic locomotor activities.
Although multiple subtypes of sodium channels are expressed in most neurons, the specific contributions of the individual sodium channels remain to be studied. The role of zebrafish Na(v)1.6 sodium channels in the embryonic locomotor movements has been investigated by the antisense morpholino (MO) knockdown. MO1 and MO2 are targeted at the regions surrounding the translation start site of zebrafish Na(v)1.6 mRNA. MO3 is targeted at the RNA splicing donor site of exon 2. The correctly spliced Na(v)1.6 mRNA of MO3 morphants is 6% relative to that of the wild-type embryos. Na(v)1.6-targeted MO1, MO2 and MO3 attenuate the spontaneous contraction, tactile sensitivity, and swimming in comparison with a scrambled morpholino and mutated MO3 morpholino. No significant defect is observed in the development of slow muscles, the axonal projection of primary motoneurons, and neuromuscular junctions. The movement impairments caused by MO1, MO2, and MO3 suggest that the function of Na(v)1.6 sodium channels is essential on the normal early embryonic locomotor activities.
Graduate Institute of Life Sciences, Tamkang University, Taipei, Taiwan.
Yau-Hung
YH
Chen
Fong-Lee
FL
Huang
Yi-Chuan
YC
Cheng
Chia-Jung
CJ
Wu
Cheng-Ning
CN
Yang
Huey-Jen
HJ
Tsay
D000818:Animals; D001483:Base Sequence; D018390:Gene Targeting; D017403:In Situ Hybridization; D008124:Locomotion / Q000235:genetics / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology; D062557:NAV1.6 Voltage-Gated Sodium Channel; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000502:physiology; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D015222:Sodium Channels; D029961:Zebrafish Proteins; C515010:scn8aa protein, zebrafish