Abstract:
:For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca(2+)-activated K(+) channels (KCa2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca(2+)-dependent. Further, the Ca(2+) dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.
journal_name
Proc Natl Acad Sci U S Aauthors
Rafizadeh S,Zhang Z,Woltz RL,Kim HJ,Myers RE,Lu L,Tuteja D,Singapuri A,Bigdeli AA,Harchache SB,Knowlton AA,Yarov-Yarovoy V,Yamoah EN,Chiamvimonvat Ndoi
10.1073/pnas.1323541111subject
Has Abstractpub_date
2014-07-08 00:00:00pages
9989-94issue
27eissn
0027-8424issn
1091-6490pii
1323541111journal_volume
111pub_type
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