Paper published by SCMH in collaboration with Imperial College and INSERM Paris.
The study co-lead by Professor Godfrey Smith, Dr Rachel Myles and Professor Radostin Simitev, School of Mathematics & Statistics, found individual heart cells from a ventricle have very different characteristics and respond to drugs in a highly variable manner; understanding these differences is key to predicting drug effects on the whole heart.
Amy J. Tibbo. Delphine Mika. Sara Dobi. Jiayue Ling. Aisling McFall.Gonzalo S. Tejeda. Connor Blair. Ruth MacLeod. Niall MacQuaide. Caglar Gök. William Fuller.
Brian O. Smith. Godfrey L. Smith. Grégoire Vandecasteele. Thomas Brand. George S. Baillie.
- POPDC1 forms a complex with type 4 phosphodiesterases (PDE4s) in cardiac myocytes.
- POPDC1 binds PDE4 enzymes in the Upstream Conserved Region 1 (UCR1) domain.
- The PDE4 binding motif within the Popeye domain lies in a region that harbours a mutation, which underpins human disease.
- Disruption of the POPDC1-PDE4 complex modulates the cycle length of spontaneous Ca2+ transients in the sinoatrial node.
- Disruption of the POPDC1-PDE4 complex causes a significant prolongation of the action potential repolarization phase.
First published: 14 January 2022