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dc.contributor.authorCrawford, Taylor R.
dc.contributor.authorTrudeau, Matthew C.
dc.descriptionPoster presented at the Society of General Physiologists, September 8, 2022en_US
dc.description.abstractTwo isoforms of the hERG (human Ether-á-go-go-Related Gene) potassium channel, hERG1a and hERG1b, associate in the heart to form the rapid delayed rectifier current (IKr), which is primarily responsible for repolarizing cardiac action potentials. Inherited mutations in both hERG1a and hERG1b cause Long QT Syndrome type 2 (LQT2), marked by prolonged cardiac repolarization and sudden death arrhythmia. The assembly of hERG1a subunits with hERG1b subunits increases the number of hERG1b subunits at the plasma membrane, but the mechanism by which hERG1a enhances hERG1b is not completely understood. Recently, it was reported that when expressed in trans, the hERG1a N-terminal region markedly increased hERG1b currents and increased biotinlabelled hERG1b protein at the plasma membrane surface. A direct structural interaction between the hERG1a N-terminal residues 216-220 and the hERG1b N-terminal region was characterized and proposed to be necessary for the upregulation of hERG1b (Johnson et al., JBC 2022). However, hERG1b channels with a deletion of the unique N-terminal 1b domain did not have a measurable increase in current density or in biotinylated protein when co-expressed with hERG1a N-terminal region pieces. This indicates that the 1b domain is required for the increase in hERG1b by hERG1a. Interestingly, the 1b domain-deleted hERG1b channels displayed a large leftward shift in the voltage dependence of activation when co-expressed with the full hERG1a N-terminal region. This is unexpected, as the 1b domain was not previously considered as a determinant of hERG gating. Here, we will investigate the mechanism of this large leftward shift and determine the role of the 1b domain in the gating properties of hERG1a/hERG1b heterotetrameric channels.en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen_US
dc.subject.meshERG1 Potassium Channelen_US
dc.subject.meshEther-A-Go-Go Potassium Channelsen_US
dc.titleDetermining the role of the unique N-terminal 1b domain in the gating of heterotetrameric hERG1a/hERG1b potassium channelsen_US

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