Electrophysiological characterization of the tetrodotoxin-resistant Na+ channel, Na(v)1.9, in mouse dorsal root ganglion neurons.
Small dorsal root ganglion neurons express preferentially the Na+ channel isoform Na(v)1.9 that mediates a tetrodotoxin-resistant (TTX-R) Na+ current. We investigated properties of the Na+ current mediated by Na(v)1.9 (I(NaN)) using the whole-cell, patch-clamp recording technique. To isolate I(NaN) from heterogeneous TTX-R Na+ currents that also contain another type of TTX-R Na+ current mediated by Na(v)1.8, we used Na(v)1.8-null mutant mice. When F- was used as an internal anion in the patch pipette solution, both the activation and inactivation kinetics for I(NaN) shifted in the hyperpolarizing direction with time. Such a time-dependent shift of the kinetics was not observed when Cl- was used as an internal anion. Functional expression of I(NaN) declined with time after cell dissociation and recovered during culture, implying that Na(v)1.9 may be regulated dynamically by trophic factors or depend on subtle environmental factors for its survival. During whole-cell recordings, the peak amplitude of I(NaN) increased dramatically after a variable delay, as if inactive or silent channels had been "kindled". Such an unusual increase of the amplitude could be prevented by adding ATP to the pipette solution or by recording with the nystatin-perforated patch-clamp technique, suggesting that the rupture of patch membrane affected the behaviour of Na(v)1.9. These peculiar properties of I(NaN) may provide an insight into the plasticity of Na+ channels that are related to pathological functions of Na+ channels accompanying abnormal pain states.
Department of Neurophysiology, Graduate School of Biomedical Sciences, Hiroshima University, 734-8551 Hiroshima, Japan.
Hiroshi
H
Maruyama
Mitsuko
M
Yamamoto
Tomoya
T
Matsutomi
Taixing
T
Zheng
Yoshihiro
Y
Nakata
John N
JN
Wood
Nobukuni
N
Ogata
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating; D051379:Mice; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000378:metabolism
D002712:Chlorides; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D020033:Protein Isoforms; C491885:Scn11a protein, mouse; D015222:Sodium Channels; D013779:Tetrodotoxin; D000255:Adenosine Triphosphate