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

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

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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-activated K channels (SK2 channel), present in a variety of cells, where they integrate changes in intracellular Ca concentration [Cai] with changes in K conductance and membrane potential, associate with L-type Ca channels; Cav1.3 and Cav1.2 through a physical bridge, α-actinin2 in cardiac myocytes. SK2 channels do not physically interact with L-type Ca channels, instead, the 2 channels colocalize via their interaction with α-actinin2 cytoskeletal protein. The association of SK2 channel with α-actinin2 localizes the channel to the entry of external Ca 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 Cav1.3 Ca channels. Null deletion of Cav1.3 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 channel, and represents the first report linking the coupling of 2 different types of ion channels via cytoskeletal proteins.

Original languageEnglish (US)
Pages (from-to)112-120
Number of pages9
JournalCirculation Research
Volume100
Issue number1
DOIs
StatePublished - Jan 2007

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Calcium-Activated Potassium Channels
Cytoskeletal Proteins
Ion Channels
Cardiac Myocytes
Membrane Potentials
Muscle Cells
Cardiac Arrhythmias

Keywords

  • α-actinin2
  • K2.2 channel
  • L-type Ca channel
  • SK2 channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via α-actinin2. / Lu, Ling; Zhang, Qian; Timofeyev, Valeriy; Zhang, Zhao; Young, J Nilas; Shin, Hee Sup; Knowlton, Anne A; Chiamvimonvat, Nipavan.

In: Circulation Research, Vol. 100, No. 1, 01.2007, p. 112-120.

Research output: Contribution to journalArticle

Lu, Ling ; Zhang, Qian ; Timofeyev, Valeriy ; Zhang, Zhao ; Young, J Nilas ; Shin, Hee Sup ; Knowlton, Anne A ; Chiamvimonvat, Nipavan. / Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via α-actinin2. In: Circulation Research. 2007 ; Vol. 100, No. 1. pp. 112-120.
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