Repository logo

Targeting p21-activated kinase 1 for development of a novel anti-arrhythmic drug class.

Published version

Published version

Repository DOI

Change log


He, Yu 
Grassam-Rowe, Alexander 


Evidence accumulated over the past decade suggests that p21-activated kinase 1 (PAK1) is a critical cardiac-protective signalling molecule. The present article provides an updated review of recent findings regarding the role of PAK1 in maintaining normal cardiac electrophysiological function through its regulation of membrane and Ca2+ clocks. We first overviewed the PAK1 activation mechanism. We then discussed recent updated results showing the action mechanisms of PAK1 signalling on Cav1.2/Cav1.3 (ICaL)-mediated Ca2+ entry, ryanodine receptor type 2-mediated sarcoplasmic reticulum (SR) Ca2+ release, transcriptional regulation of SR Ca2+-ATPase 2a, Na+/Ca2+ exchangers, and Ca2+/calmodulin-dependent protein kinase II. Finally, we proposed a new and exciting route for developing a PAK1-based therapeutic strategy for cardiac arrhythmias. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.


Peer reviewed: True


Ca2+ clock, FTY720, arrhythmia, membrane clock, p21-activated kinase 1, protein phosphatase 2A, Anti-Arrhythmia Agents, p21-Activated Kinases, Heart, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Calcium-Calmodulin-Dependent Protein Kinases, Calcium, Phosphorylation

Journal Title

Philos Trans R Soc Lond B Biol Sci

Conference Name

Journal ISSN


Volume Title


The Royal Society
British Heart Foundation (British Heart Foundation (BHF) (BHF Centre for Res)