哺乳類のナトリウムチャネルの毛穴内のイオン結合部位の分子局所化

P H Backx¹, D T Yue, J H Lawrence

¹Department of Medicine, Johns Hopkins University, Baltimore, MD 21205.

Science (New York, N.Y.)

|July 10, 1992

まとめ

カドミウムイオンはナトリウムチャネルを遮断し,骨格筋のチャネルよりも心臓のチャネルへの親和性が高くなります. 特定の突然変異が,この感受性を変化させ,チャネルポールの重要な残留物を明らかにした.

科学分野:

バイオフィジックス生物物理学
分子生物学は分子生物学である.
薬理学薬理学とは

背景:

ナトリウムチャネルは,様々な組織における細胞刺激性にとって極めて重要です.
カドミウムイオンは,ナトリウムチャネルと相互作用し,それをブロックすることが知られている.
テトロドトキシン (TTX) は,ナトリウムチャネルサブタイプを区別するために使用される特定のブロッカーです.

研究の目的:

カドミウムイオンによるナトリウムチャネルイソフォームの微分阻害を調査する.
カドミウム結合とチャネル機能における特定の残留物の役割を決定する.
カドミウムの結合部位をナトリウムチャネル孔内に定着させるため.

主な方法:

カドミウムイオン阻害を分析するために化学反応速度理論を利用した.
試験された野生型および変異性ナトリウムチャネル,心臓および骨格筋の異形を含む.
カドミウムとテトロドトキシン (TTX) がチャネル活動に及ぼす影響を調査した.

主要な成果:

カドミウムは,TTXに敏感な骨格筋イソフォームと比較して,TTXに抵抗する心臓のナトリウムチャネルに対して,著しく高い親和性を示した.
骨格筋チャネルにおける変異 (Tyr401からCys) は,カドミウムに対する心臓チャネル感受性を模倣したが,TTX耐性を授与した.
カドミウム結合部位は,毛穴の電場深さの約20%に位置していた.

結論:

特定のアミノ酸残留は,ナトリウムチャネルがカドミウムに対して有異な感受性を決定する.
特定された重要な残留物は,ナトリウムチャネルの孔構造とイオン浸透において重要な役割を果たします.
この研究は,重金属によるナトリウムチャネル調節の分子機構の洞察を提供します.

さらに関連する動画

11:13

Indirect Immunofluorescence on Frozen Sections of Mouse Mammary Gland

Published on: December 1, 2015

11:31

Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands

Published on: May 30, 2017

関連する概念動画

01:19

Contact-dependent Signaling

Contact-dependent signaling, as the name suggests, requires that communicating cells be in direct contact with each other. This is achieved either through receptor-ligand interactions or by specialized cytoplasmic channels that allow the flow of small molecules between cells. In animal cells, channels called gap junctions facilitate contact-dependent signaling in certain tissues, whereas, plasmodesmata perform a similar function in plants.
Gap Junctions
In animal cells, gap junctions are formed...

01:37

Gap Junctions

Multicellular organisms employ a variety of ways for cells to communicate with each other. Gap junctions are specialized proteins that form pores between neighboring cells in animals, connecting the cytoplasm between the two, and allowing for the exchange of molecules and ions. They are found in a wide range of invertebrate and vertebrate species, mediate numerous functions including cell differentiation and development, and are associated with numerous human diseases, including cardiac and...

00:59

Mechanisms of Membrane Domain Formation

Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...

01:28

Protein Translocation Machinery on the ER Membrane

The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.

01:29

Tight Junctions

Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...

01:27