ヒト錐体細胞 cGMP 依存性陽イオンチャネル機能の電気生理学的検討； 杆体一色型色覚における遺伝子変異の検索・機能解析

• 岡田 明

  滋賀医大・医・眼科

• 上山 久雄

  滋賀医大・医・生化２

• 豊田 太

  滋賀医大・医・生理２

• 丁 維光

  滋賀医大・医・生理２

• 小田 早苗

  滋賀医大・医・眼科

• 山出 Shinichi

  滋賀医大・医・眼科

• 松浦 博

  滋賀医大・医・生理２

書誌事項

タイトル別名

• Functional role of the hCNGB3 in regulation of human cone CNG channel: effect of rod monochromacy-associated mutations in hCNGB3 on channel function

抄録

[PURPOSE] The human cone photoreceptor CNG channel is thought to comprise hCNGA3- and hCNGB3-subunits. The purpose was to examine functional role of hCNGB3 in modulation of human cone CNG channels and to characterize functional consequences of rod monochromacy-associated mutations in hCNGB3 (S435F and D633G). [METHODS] Macroscopic patch currents were recorded from HEK293 cells expressing homomeric and heteromeric channels using inside-out patch-clamp technique. [RESULTS] Both hCNGA3 homomeric and hCNGA3/hCNGB3 heteromeric channels were activated by cGMP, with K_1/2 of 11.1±1.0 and 26.2±1.9 μM, respectively. The hCNGA3 channels appeared to be more sensitive to inhibition by extracellular Ca²⁺ compared with hCNGA3/hCNGB3 channels. Coexpression of either of rod monochromacy-associated mutants of hCNGB3 with hCNGA3 significantly reduced K_1/2 value for cGMP but little affected the sensitivity to extracellular Ca²⁺, compared with wild-type heteromeric channels. The selectivity of homomeric and heteromeric channels for monovalent cations was largely similar. Immunoprecipitation experiments showed association of hCNGA3-subunit with both of wild-type and mutant hCNGB3-subunits. [CONCLUSIONS] The rod monochromacy-associated S435F and D633G mutations in hCNGB3 evokes a significant increase in the apparent affinity for cGMP, which should alter cone function and thereby contribute at least partly to pathogenesis of the disease. [Jpn J Physiol 54 Suppl:S136 (2004)]

収録刊行物

• 日本生理学会大会発表要旨集

  日本生理学会大会発表要旨集 2004 (0), S136-S136, 2004

  一般社団法人　日本生理学会

キーワード

• cone photoreceptor
• cGMP-gated cation channel
• patch-clamp technique
• rod monochromacy

詳細情報

• CRID: 1390282680706653824
• NII論文ID: 130005446948
• DOI: 10.14849/psjproc.2004.0_s136_4
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可