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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1851    most recent 01045.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Abi-Char, J. Articles by Hatem, S. N. Search for Related Content PubMed PubMed Citation Articles by Abi-Char, J. Articles by Hatem, S. N.

The anchoring protein SAP97 retains Kv1.5 channels in the plasma membrane of cardiac myocytes

¹Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche (UMR) S621, Paris; ²Université Pierre et Marie Curie-Paris 6, UMR S621, Paris; ³INSERM, UMR 698, Paris; and ⁴Université Denis Diderot-Paris 7, Paris, France

Submitted 8 September 2007 ; accepted in final form 29 January 2008

Membrane- associated guanylate kinase proteins (MAGUKs) are important determinants of localization and organization of ion channels into specific plasma membrane domains. However, their exact role in channel function and cardiac excitability is not known. We examined the effect of synapse-associated protein 97 (SAP97), a MAGUK abundantly expressed in the heart, on the function and localization of Kv1.5 subunits in cardiac myocytes. Recombinant SAP97 or Kv1.5 subunits tagged with green fluorescent protein (GFP) were overexpressed in rat neonatal cardiac myocytes and in Chinese hamster ovary (CHO) cells from adenoviral or plasmidic vectors. Immunocytochemistry, fluorescence recovery after photobleaching, and patch-clamp techniques were used to study the effects of SAP97 on the localization, mobility, and function of Kv1.5 subunits. Adenovirus-mediated SAP97 overexpression in cardiac myocytes resulted in the clustering of endogenous Kv1.5 subunits at myocyte-myocyte contacts and an increase in both the maintained component of the outward K⁺ current, I_Kur (5.64 ± 0.57 pA/pF in SAP97 myocytes vs. 3.23 ± 0.43 pA/pF in controls) and the number of 4-aminopyridine-sensitive potassium channels in cell-attached membrane patches. In live myocytes, GFP-Kv1.5 subunits were mobile and organized in clusters at the basal plasma membrane, whereas SAP97 overexpression reduced their mobility. In CHO cells, Kv1.5 channels were diffusely distributed throughout the cell body and freely mobile. When coexpressed with SAP97, Kv subunits were organized in plaquelike clusters and poorly mobile. In conclusion, SAP97 regulates the K⁺ current in cardiac myocytes by retaining and immobilizing Kv1.5 subunits in the plasma membrane. This new regulatory mechanism may contribute to the targeting of Kv channels in cardiac myocytes.

potassium channel; membrane-associated guanylate kinase proteins; fluorescence recovery after photobleaching

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