Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Phosphorylation of the I Ks Novel Mechanism Underlying Variable Antiarrhythmic Drug Actions

Phosphorylation of the I Ks Novel Mechanism Underlying Variable Antiarrhythmic Drug Actions Brief Rapid Communication Phosphorylation of the I Channel Complex Inhibits Ks Drug Block Novel Mechanism Underlying Variable Antiarrhythmic Drug Actions Tao Yang, PhD; Hideaki Kanki, MD, PhD; Dan M. Roden, MD Background—I , an important repolarizing current in heart, is an antiarrhythmic drug target and is markedly increased by Ks activation of protein kinase A (PKA; eg, by -adrenergic stimulation). Because -adrenergic stimulation is a frequent trigger of arrhythmias, we hypothesized that PKA stimulation inhibits drug block. Methods and Results—CHO cells were transfected with KCNQ1 cDNA (encoding the pore-forming subunit) with or without the ancillary subunit KCNE1. IC for quinidine block of basal I was 5.81.2 mol/L, versus 19.93.2 50 Ks mol/L (P0.01) for PKA-stimulated current. A similar 3-fold shift was apparent in the absence of KCNE1 and with the I -specific blocker chromanol 293B. The first current recorded after channels were held at rest and exposed to the Ks drug was reduced 40%, and further depolarizations increased the block with a time constant ()of18127 seconds. By contrast, PKA-stimulated channels displayed a 5% first-pulse block and much slower block development (40585 seconds). Alanine substitution at 3 potential PKA target sites (S27, S468, and T470) generated an I that Ks http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Circulation Wolters Kluwer Health

Phosphorylation of the I Ks Novel Mechanism Underlying Variable Antiarrhythmic Drug Actions

Roden, Dan M.
Circulation , Volume 108 (2) – Jul 1, 2003
Download PDF
3 pages

Loading next page...
 
/lp/wolters-kluwer-health/phosphorylation-of-the-i-ks-novel-mechanism-underlying-variable-MfrvFIX30Z

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

ISSN
0009-7322
eISSN
1524-4539
DOI
10.1161/01.CIR.0000082708.86266.B8
pmid
12835205
Publisher site
See Article on Publisher Site

Abstract

Brief Rapid Communication Phosphorylation of the I Channel Complex Inhibits Ks Drug Block Novel Mechanism Underlying Variable Antiarrhythmic Drug Actions Tao Yang, PhD; Hideaki Kanki, MD, PhD; Dan M. Roden, MD Background—I , an important repolarizing current in heart, is an antiarrhythmic drug target and is markedly increased by Ks activation of protein kinase A (PKA; eg, by -adrenergic stimulation). Because -adrenergic stimulation is a frequent trigger of arrhythmias, we hypothesized that PKA stimulation inhibits drug block. Methods and Results—CHO cells were transfected with KCNQ1 cDNA (encoding the pore-forming subunit) with or without the ancillary subunit KCNE1. IC for quinidine block of basal I was 5.81.2 mol/L, versus 19.93.2 50 Ks mol/L (P0.01) for PKA-stimulated current. A similar 3-fold shift was apparent in the absence of KCNE1 and with the I -specific blocker chromanol 293B. The first current recorded after channels were held at rest and exposed to the Ks drug was reduced 40%, and further depolarizations increased the block with a time constant ()of18127 seconds. By contrast, PKA-stimulated channels displayed a 5% first-pulse block and much slower block development (40585 seconds). Alanine substitution at 3 potential PKA target sites (S27, S468, and T470) generated an I that Ks

Journal

Circulation – Wolters Kluwer Health

Published: Jul 1, 2003

There are no references for this article.