Molecular Coupling of a Ca 2+ -Activated K + Channel to L-Type Ca 2+ Channels via α-Actinin2

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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 Ca2+-activated K+ channels (SK2 channel), present in a variety of cells, where they integrate changes in intracellular Ca2+ concentration [Ca2+i] with changes in K+ conductance and membrane potential, associate with L-type Ca2+ channels; Cav1.3 and Cav1.2 through a physical bridge, α-actinin2 in cardiac myocytes. SK2 channels do not physically interact with L-type Ca2+ 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 Ca2+ 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 Ca2+ channels. Null deletion...