This Research Topic encompasses two parts - both related to autonomic regulation of the heart.
Part 1: Emerging Regulators – Cardiac and Neuronal RGS proteins
(Craig Doupnik)
The extent of vagal acetylcholine release at cardiac cells represents the classic process described by Otto Loewi nearly a century ago for establishing parasympathetic ‘tone' on the heart. Recent studies have identified new cardiac components of the signal transduction machinery that work to effectively dampen and accelerate the incoming muscarinic response. Regulators of G protein Signaling 4 and 6, RGS4 and RGS6 respectively, both are expressed in sinoatrial pacemaker cells and genetic ablation in mice indicate both work to suppress muscarinic sensitivity and parasympathetic tone. The findings that 2 different cardiac RGS proteins participate in setting the parasympathetic tone suggests genetic redundancy in regulating this key signaling pathway. Moreover, neuronally expressed RGS proteins might also be expected to affect upstream levels of both sympathetic and parasympathetic outflow, as well as output of the intrinsic epicardial nervous system. RGS redundancy has obvious benefits as a species survival strategy, particularly when applied towards vital functions like maintaining optimal cardiac performance. Yet redundancy presents a challenge for drug designers given the limited efficacy of targeting a specific RGS protein. This 'Research Topic' series will explore how RGS proteins share common yet distinct roles at multiple levels controlling autonomic regulation of heart function, and what critical questions remain for translational researchers examining the role of these pathways in conditions such as atrial fibrillation, where RGS proteins are currently being assessed as potential druggable targets
Part 2: Beta-adrenergic stimulation and arrhythmogenesis (Peter Taggart)
Why any particular premature beat should be harmless and yet another one fatal? It remains an unanswered question of major importance. End stage disease is not the answer, as many resuscitated victims of VF arrest continue to live for many years often with no further arrhythmic events. A likely explanation is that physiological properties involved in the underlying mechanisms are subject to biological fluctuation and the arrhythmic episode is the result of co-existence at a particular moment in time of an appropriate trigger and substrate.
The autonomic nervous system exerts a constant minute to minute modulatory effect on the cardiac electrophysiology and is well known to play an important role in arrhythmogenesis. Considerable progress continues to be made in our understanding of the role of beta-adrenergic stimulation in arrhythmogenesis from the subcellular to the in vivo human heart. The purpose of this RT is to examine current knowledge at all levels, molecular to whole heart, in the light of experimental evidence, theoretical implications and modelling.
This Research Topic encompasses two parts - both related to autonomic regulation of the heart.
Part 1: Emerging Regulators – Cardiac and Neuronal RGS proteins
(Craig Doupnik)
The extent of vagal acetylcholine release at cardiac cells represents the classic process described by Otto Loewi nearly a century ago for establishing parasympathetic ‘tone' on the heart. Recent studies have identified new cardiac components of the signal transduction machinery that work to effectively dampen and accelerate the incoming muscarinic response. Regulators of G protein Signaling 4 and 6, RGS4 and RGS6 respectively, both are expressed in sinoatrial pacemaker cells and genetic ablation in mice indicate both work to suppress muscarinic sensitivity and parasympathetic tone. The findings that 2 different cardiac RGS proteins participate in setting the parasympathetic tone suggests genetic redundancy in regulating this key signaling pathway. Moreover, neuronally expressed RGS proteins might also be expected to affect upstream levels of both sympathetic and parasympathetic outflow, as well as output of the intrinsic epicardial nervous system. RGS redundancy has obvious benefits as a species survival strategy, particularly when applied towards vital functions like maintaining optimal cardiac performance. Yet redundancy presents a challenge for drug designers given the limited efficacy of targeting a specific RGS protein. This 'Research Topic' series will explore how RGS proteins share common yet distinct roles at multiple levels controlling autonomic regulation of heart function, and what critical questions remain for translational researchers examining the role of these pathways in conditions such as atrial fibrillation, where RGS proteins are currently being assessed as potential druggable targets
Part 2: Beta-adrenergic stimulation and arrhythmogenesis (Peter Taggart)
Why any particular premature beat should be harmless and yet another one fatal? It remains an unanswered question of major importance. End stage disease is not the answer, as many resuscitated victims of VF arrest continue to live for many years often with no further arrhythmic events. A likely explanation is that physiological properties involved in the underlying mechanisms are subject to biological fluctuation and the arrhythmic episode is the result of co-existence at a particular moment in time of an appropriate trigger and substrate.
The autonomic nervous system exerts a constant minute to minute modulatory effect on the cardiac electrophysiology and is well known to play an important role in arrhythmogenesis. Considerable progress continues to be made in our understanding of the role of beta-adrenergic stimulation in arrhythmogenesis from the subcellular to the in vivo human heart. The purpose of this RT is to examine current knowledge at all levels, molecular to whole heart, in the light of experimental evidence, theoretical implications and modelling.
