Mechanisms of Action of the KCa2-Negative Modulator AP30663, a Novel Compound in Development for Treatment of Atrial Fibrillation in Man

Autor: Bo Hjorth Bentzen, Sofia Hammami Bomholtz, Rafel Simó-Vicens, Lasse Folkersen, Lea Abildgaard, Tobias Speerschneider, Kalai Mangai Muthukumarasamy, Nils Edvardsson, Ulrik S. Sørensen, Morten Grunnet, Jonas Goldin Diness

Publikováno v: Frontiers in Pharmacology, Vol 11 (2020)

AimsSmall conductance Ca2+-activated K+ channels (SK channels, KCa2) are a new target for treatment of atrial fibrillation (AF). AP30663 is a small molecule inhibitor of KCa2 channels that is currently in clinical development for treatment of AF. The

Externí odkaz: https://doaj.org/article/f462fdae02ad4e698282f8bd9227d4e9

The KCa2 Channel Inhibitor AP14145, But Not Dofetilide or Ondansetron, Provides Functional Atrial Selectivity in Guinea Pig Hearts

Autor: Jeppe Egedal Kirchhoff, Mark Alexander Skarsfeldt, Kalai Mangai Muthukumarasamy, Rafel Simó-Vicens, Sofia Hammami Bomholtz, Lea Abildgaard, Thomas Jespersen, Ulrik S. Sørensen, Morten Grunnet, Bo Hjorth Bentzen, Jonas Goldin Diness

Publikováno v: Frontiers in Pharmacology, Vol 10 (2019)

Background and Purpose: Prolongation of cardiac action potentials is considered antiarrhythmic in the atria but can be proarrhythmic in ventricles if the current carried by Kv11.1-channels (IKr) is inhibited. The current mediated by KCa2-channels, IK

Externí odkaz: https://doaj.org/article/0dc2f2226e674b7996e9529f482bfbcc

Impact of arrhythmogenic calmodulin variants on small conductance Ca2+‐activated K+ (SK3) channels

Autor: Martin W. Berchtold, Thomas Jespersen, Jonas M. la Cour, Kalai Mangai Muthukumarasamy, Arnela Saljic, Kim Boddum, Morten Grunnet

Publikováno v: Physiological Reports, Vol 7, Iss 19, Pp n/a-n/a (2019)
Saljic, A, Muthukumarasamy, K M, la Cour, J M, Boddum, K, Grunnet, M, Berchtold, M W & Jespersen, T 2019, ' Impact of arrhythmogenic calmodulin variants on small conductance Ca 2+-activated K + (SK3) channels ', Physiological Reports, vol. 7, no. 19, e14210 . https://doi.org/10.14814/phy2.14210

Calmodulin (CaM) is a ubiquitous Ca2+‐sensing protein regulating many important cellular processes. Several CaM‐associated variants have been identified in a small group of patients with cardiac arrhythmias. The mechanism remains largely unknown,

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfe47b75838c954785a1498a0896531e
https://doaj.org/article/03d575e3576a47a9ba14a907dda893e0