4. Pathological remodelling of H+ ion signalling and control
A large fall of pHi is prominent in myocardial ischaemia, where it causes acute contractile failure, abnormal Ca2+ signalling and arrhythmia. We have a particular interest in understanding how changes in pHi influence the probability and properties of pro-arrhythmic Ca2+ waves, both via direct effects on Ca2+-handling proteins such as the ryanodine receptor, and indirectly via effects on Na+i.
We have increasing evidence for a fundamental remodelling of the pHi regulatory system in maladaptive hypertrophy and heart failure, which may contribute to alterations in Ca2+ handling. Such changes in Ca2+ handling have long been considered to play a causal role in the development of these pathologies, contributing to changes in gene expression as well as in contractility and electrical behaviour. Therefore we are actively pursuing research into a link between pH dysregulation and development of hypertrophy and heart failure. This work is funded by a 5-year British Heart Foundation Programme Grant.