TAILIEUCHUNG - Báo cáo khoa học: KCNE4 can co-associate with the IKs (KCNQ1–KCNE1) channel complex

Voltage-gated potassium (KV) channels can form heteromultimeric com-plexes with a variety of accessory subunits, including KCNE proteins. Het-erologous expression studies have demonstrated diverse functional effects of KCNE subunits on several KV channels, including KCNQ1 () that, together with KCNE1, generates the slow-delayed rectifier current (IKs) important for cardiac repolarization. | ễFEBS Journal KCNE4 can co-associate with the IKs KCNQ1-KCNE1 channel complex Lauren J. Manderfield1 and Alfred L. George Jr1 2 1 Department of Pharmacology Vanderbilt University Nashville TN USA 2 Department of Medicine Vanderbilt University Nashville TN USA Keywords accessory subunits KCNE4 KCNQ1 potassium channel Correspondence A. L. George Jr 529 Light Hall 2215 Garland Avenue Nashville TN 37232-0275 USA Fax 1 615 936 2661 Tel 1 615 936 2660 E-mail Received 24 August 2007 revised 11 December 2007 accepted 15 January 2008 doi Voltage-gated potassium KV channels can form heteromultimeric complexes with a variety of accessory subunits including KCNE proteins. Heterologous expression studies have demonstrated diverse functional effects of KCNE subunits on several KV channels including KCNQ1 that together with KCNE1 generates the slow-delayed rectifier current IKs important for cardiac repolarization. In particular KCNE4 exerts a strong inhibitory effect on KCNQ1 and other KV channels raising the possibility that this accessory subunit is an important potassium current modulator. A polyclonal KCNE4 antibody was developed to determine the human tissue expression pattern and to investigate the biochemical associations of this protein with KCNQ1. We found that KCNE4 is widely and variably expressed in several human tissues with greatest abundance in brain liver and testis. In heterologous expression experiments immunoprecipitation followed by immunoblotting was used to establish that KCNE4 directly associates with KCNQ1 and can co-associate together with KCNE1 in the same KCNQ1 complex to form a triple subunit complex KCNE1-KCNQ1-KCNE4 . We also used cell surface biotinylation to demonstrate that KCNE4 does not impair plasma membrane expression of either KCNQ1 or the triple subunit complex indicating that biophysical mechanisms probably underlie the inhibitory effects of KCNE4. The observation that .

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