Sam Bose

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting around 2% of the population in Europe and the USA, rising to 5% in populations over the age of 65. AF is a major cause of heart failure and significantly increases the risk of stroke. The underlying mechanisms that can lead to AF are still largely unknown. As a result, current pharmacological interventions used for the treatment of AF are often non-specific and can lead to an increased risk of off-target effects, including in the ventricles where they can increase the risk of potentially fatal ventricular arrhythmias.

My research, which is supported by a grant from the British Heart Foundation, is focussed on identifying atrial specific pathways that may provide a suitable target for the development of treatments for AF without resulting in ventricular side effects. In particular, my research investigates the downstream events that occur as a result of inositol­ trisphosphate (IP₃) signalling in atrial myocytes. IP₃ is a calcium mobilising second messenger that acts via IP₃ receptors (IP₃R) on the sarcoplasmic reticulum. IP₃R expression is significantly increased in patients with AF, and activation of the pathway can lead to an increase in potentially arrhythmogenic diastolic calcium release. Interestingly, expression of IP₃R type 2 is at least six times greater in atrial compared to ventricular myocytes, raising the possibility that the IP₃ pathway may be a suitable target for the development of atrial selective treatments.

My work involves the use of a range of techniques to investigate IP₃ signalling, from the level of the whole tissue down to intracellular events and molecular interactions. This includes the use of electrophysiological patch-clamp recordings, live-cell calcium imaging, high resolution microscopy, immunocytochemistry and molecular biology.