Cyclic guanosine 3′,5′‐monophosphate (cGMP) signalling in cardiomyocytes is intricately organized within cellular compartments, influencing several physiological and pathophysiological processes in the heart. We review how compartmented cGMP signalling is regulated and can be monitored within cardiomyocytes, emphasizing recent advances and methodologies. Three different guanylyl cyclases (GCs), two particulate (GC‐A and GC‐B) and one soluble (sGC), produce distinct cGMP pools, giving rise to differential signalling in cardiomyocytes. Phosphodiesterases (PDEs) maintain intracellular cGMP gradients. The use of intracellular biosensors, particularly those based on fluorescence resonance energy transfer (FRET), has enabled visualization of cGMP dynamics with high spatial and temporal resolution. These tools, which are constantly being improved, allow the observation of localized cGMP signals and have revealed discrete signalling compartments regulated by the subcellular localization of GCs and PDEs. Understanding these complex signalling networks in cardiomyocytes of healthy and diseased hearts can guide potential therapeutic approaches to treat cardiac dysfunction, including hypertrophy and heart failure. In conclusion, new tools are refining our understanding of compartmented cGMP signalling, which may lead to novel strategies for targeted therapeutic interventions in cardiovascular diseases.
Andressen et al. (Sat,) studied this question.