Molecular Coupling of a Ca super(2+)-Activated K super(+) Channel to L-Type Ca super(2+) Channels via alpha -Actinin2
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 super(2+)-activated K super(+) channels (SK2 channel), present in a v...
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Published in | Circulation research Vol. 100; no. 1; pp. 112 - 120 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
05.01.2007
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Online Access | Get full text |
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Summary: | 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 super(2+)-activated K super(+) channels (SK2 channel), present in a variety of cells, where they integrate changes in intracellular Ca super(2+) concentration [Ca super(2+) sub(i)] with changes in K super(+) conductance and membrane potential, associate with L-type Ca super(2+) channels; Ca sub(v)1.3 and Ca sub(v)1.2 through a physical bridge, alpha -actinin2 in cardiac myocytes. SK2 channels do not physically interact with L-type Ca super(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 super(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 sub(v)1.3 Ca super(2+) channels. Null deletion of Ca sub(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 super(2+) channel, and represents the first report linking the coupling of 2 different types of ion channels via cytoskeletal proteins. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 0009-7330 1524-4571 |