Publication Date:
1990-11-02
Description:
Voltage-gated sodium channels are transmembrane proteins of approximately 2000 amino acids and consist of four homologous domains (I through IV). In current topographical models, domains III and IV are linked by a highly conserved cytoplasmic sequence of amino acids. Disruptions of the III-IV linker by cleavage or antibody binding slow inactivation, the depolarization-induced closed state characteristic of sodium channels. This linker might be the positively charged "ball" that is thought to cause inactivation by occluding the open channel. Therefore, groups of two or three contiguous lysines were neutralized or a glutamate was substituted for an arginine in the III-IV linker of type III rat brain sodium channels. In all cases, inactivation occurred more rapidly rather than more slowly, contrary to predictions. Furthermore, activation was delayed in the arginine to glutamate mutation. Hence, the III-IV linker does not simply act as a charged blocker of the channel but instead influences all aspects of sodium channel gating.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moorman, J R -- Kirsch, G E -- Brown, A M -- Joho, R H -- HL-36930/HL/NHLBI NIH HHS/ -- KL-01858/PHS HHS/ -- NS-23877/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1990 Nov 2;250(4981):688-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Texas Medical Branch, Galveston 77550.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2173138" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Cytoplasm/physiology
;
Molecular Sequence Data
;
*Mutation
;
RNA, Messenger/analysis
;
Sodium Channels/chemistry/genetics/*physiology
;
Structure-Activity Relationship
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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