ArticleNaunyn-Schmiedeberg's archives of pharmacology2009
The transmembrane beta-subunits KCNE1, KCNE2, and DPP6 modify pharmacological effects of the antiarrhythmic agent tedisamil on the transient outward current Ito.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Beyond the Alpha Subunit: Pharmacological Modulation of Kv4.2 Channels by Ancillary Proteins.Cells · 2026Review
- Auxiliary subunits control biophysical properties and response to compound NS5806 of the Kv4 potassium channel complex.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Arrhythmogenic KCNE gene variants: current knowledge and future challenges.Frontiers in genetics · 2014Review
- Unique cardiac Purkinje fiber transient outward current β-subunit composition: a potential molecular link to idiopathic ventricular fibrillation.Circulation research · 2013Article
- KCNQ1 subdomains involved in KCNE modulation revealed by an invertebrate KCNQ1 orthologue.The Journal of general physiology · 2011Article
- Effect of the I(to) activator NS5806 on cloned K(V)4 channels depends on the accessory protein KChIP2.British journal of pharmacology · 2010Article
- Propranolol regulates cardiac transient outward potassium channel in rat myocardium via cAMP/PKA after short-term but not after long-term ischemia.Naunyn-Schmiedeberg's archives of pharmacology · 2010Article
- Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation.Journal of molecular and cellular cardiology · 2010Review
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accessory beta-subunits modulate the pharmacology of ion channel blockers. The aim was to investigate differences in effects of the antiarrhythmic agent and open-channel blocker tedisamil on transient outward current I(to) (Kv4.3) when coexpressed with beta-subunits potassium voltage-gated channel, Isk-related family, member 1 (KCNE1), potassium voltage-gated channel, Isk-related family, member 2 (KCNE2), or dipeptidyl-aminopeptidase-like protein 6 (DPP6) which modulate I(to) kinetics. Tedisamil inhibited I(to) with IC(50) values of 16 microM for Kv4.3+KChIP2, 11 microM in the presence of KCNE1, and 14 microM for KCNE2. Values were higher in the presence of DPP6 or DPP6+KCNE2 (35 and 26 microM). K(d) values of tedisamil binding and rate constants were not affected by KCNE or DPP6. I(to) kinetics were accelerated by KCNE and DPP6, inactivation to a larger extent with DPP6. Tedisamil did not affect activation time course but apparently accelerated inactivation in all channel subunit combinations tested. Deletion of the intracellular domain of KCNE2 or DPP6 resulted in slowing of kinetics and increased tedisamil sensitivity (IC(50) 4 and 7 microM). It is concluded that apparent effects of DPP6 and deletion mutants (KCNE2 and DPP6) are due to the acceleration or slowing effects of the beta-subunits on I(to) kinetics.
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