Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2.

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Abstract Text:

Ling Lu,Qian Zhang,Valeriy Timofeyev,Zhao Zhang,J Nilas Young,Hee-Sup Shin,Anne A Knowlton,Nipavan Chiamvimonvat,

Cytoskeletal proteins are known to sculpt the structural architecture of cells. However, their role as bridges linking the functional crosstalk of different ion channels is unknown. Here, we demonstrate that a small conductance Ca(2+)-activated K(+) channels (SK2 channel), present in a variety of cells, where they integrate changes in intracellular Ca(2+) concentration [Ca(2+)(i)] with changes in K(+) conductance and membrane potential, associate with L-type Ca(2+) channels; Ca(v)1.3 and Ca(v)1.2 through a physical bridge, alpha-actinin2 in cardiac myocytes. SK2 channels do not physically interact with L-type Ca(2+) channels, instead, the 2 channels colocalize via their interaction with alpha-actinin2 cytoskeletal protein. The association of SK2 channel with alpha-actinin2 localizes the channel to the entry of external Ca(2+) source, which regulate the channel function. Furthermore, we demonstrated that the functions of SK2 channels in atrial myocytes are critically dependent on the normal expression of Ca(v)1.3 Ca(2+) channels. Null deletion of Ca(v)1.3 channel results in abnormal function of SK2 channel and prolongation of repolarization and atrial arrhythmias. Our study provides insight into the molecular mechanisms of the coupling of SK2 channel with voltage-gated Ca(2+) channel, and represents the first report linking the coupling of 2 different types of ion channels via cytoskeletal proteins.

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Publishing Authors By Initials

L Lu,Q Zhang,V Timofeyev,Z Zhang,JN Young,HS Shin,AA Knowlton,N Chiamvimonvat,

For similar investigative techniques: genetic techniques: cloning, molecular: two-hybrid system techniques research abstracts see: investigative techniques: genetic techniques: cloning, molecular: two-hybrid system techniques research

PUBMED ID PMID:

MEDLINE DATE:

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Circulation research

VOLUME: 100

Page Numbers: 112-20

Journal Abbreviation: Circ. Res.

ISSN: 1524-4571

DAY: 16

MONTH: 11

YEAR: 2006

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 47103

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Keywords Mesh Terms:

KEYWORDS: Two-Hybrid System Techniques

MESH TERMS: physiology

Chemical & Substance for Abstract: Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2. Information

Substance Name: Actinin

Registry Number: 11003-00-2

Grant and Affiliation Information for Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2.

AFFILIATION: Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, One Shields Avenue, GBSF 6315, Davis, CA 95616, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL77281

ACRONYM: HL

MEDLINETA: Circ Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2 Related Publications

• Drug-induced long QT syndrome: a continuing challenge in the field.
• Functional roles of a Ca2+-activated k+ channel in atrioventricular nodes.
• IK1 and cardiac hypoxia: after the long and short QT syndromes, what else can go wrong with the inward rectifier K+ currents?
• Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2.
• Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors.