Ankyrin-G regulates inactivation gating of the neuronal sodium channel, Nav1.6.
Ankyrin-G, a modular protein, plays a critical role in clustering voltage-gated sodium channels (Nav channels) in nodes of Ranvier and initial segments of mammalian neurons. However, direct effects of ankyrin-G on electrophysiological properties of Nav channels remain elusive. In this study, we explored whether ankyrin-G has a role in modifying gating properties of the neuronal Nav1.6 channel that is predominantly localized at nodes of Ranvier and initial segments. TsA201 cells transfected with the human Nav1.6 cDNA alone exhibited significant persistent sodium current (Ina-p). On the other hand, Ina-p was barely detected on co-expression with ankyrin-G. Ankyrin-B, another ankyrin, did not show such an effect. Expression of chimeras between the two isoforms of ankyrin suggests that the membrane-binding domain of ankyrin-G is critical for reducing the Ina-p of Nav1.6. These results suggest that ankyrin-G regulates neuronal excitability not only through clustering Nav channels but also by directly modifying their channel gating.
Shirahata
Emi
E
Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.
Iwasaki
Hirohide
H
Takagi
Masahiro
M
Lin
Changqing
C
Bennett
Vann
V
Okamura
Yasushi
Y
Hayasaka
Kiyoshi
K
D017487:Ankyrins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers; D005071:Evoked Potentials / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008969:Molecular Sequence Data; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
C498994:ANK2 protein, human; C490613:ANK3 protein, human; D017487:Ankyrins; D017931:DNA Primers; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C100681:SCN8A protein, human; D015222:Sodium Channels; D013779:Tetrodotoxin