Title: A K+ channel splice variant common in human heart lacks a C-terminal domain required for expression of rapidly activating delayed rectifier current
Authors: Kupershmidt, S ×
Snyders, DJ
Raes, Adam
Roden, DM #
Issue Date: Oct-1998
Publisher: Amer soc biochemistry molecular biology inc
Series Title: Journal of Biological Chemistry vol:273 issue:42 pages:27231-27235
Abstract: We have cloned HERG(USO), a C-terminal splice variant of the human ether-g-go-go-related gene (HERG), the gene encoding the rapid component of the delayed rectifier (I-Kr), from human heart, and we find that its mRNA is similar to 2-fold more abundant than that for HERG(1) (the originally described cDNA). After transfection of HERG(USO) in Ltk(-) cells, no current was observed, However, coexpression of HERG(USO) with HERG(1) modified I-Kr by decreasing its amplitude, accelerating its activation, and shifting the voltage dependence of activation 8.8 mV negative. As with HERG(USO), HERG(Delta C) (a HERG(1), construct lacking the C-terminal 462 amino acids) also produced no current in transfected cells. However, I-Kr was rescued by ligation of 104 amino acids from the C terminus of HERG(1) to the C terminus of HERG(Delta C), indicating that the C terminus of HERG(1) includes a domain (less than or equal to 104 amino acids) that is critical for faithful recapitulation of I-Kr. The lack of this C-terminal domain not only explains the finding that HERG(USO) does not generate I-Kr but also indicates a similar mechanism for hitherto-uncharacterized long QT syndrome HERG mutations that disrupt the splice site or the C-terminal. We suggest that the amplitude and gating of cardiac I-Kr depends on expression of both HERG(1) and HERG(USO).
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
× corresponding author
# (joint) last author

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