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Dysrhythmias/Channelopathies and Signaling Pathways

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Signaling in the Heart

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Abstract

Cardiac dysrhythmias remain an important cause of morbidity and mortality around the world. Notwithstanding the recent scientific advances in genetic analysis to assign a risk stratification for many of the dysrhythmogenic syndromes, we should take into account the numerous and important epigenetic modifiers/modulator factors, including family history, gender, repolarization abnormalities, and sympathetic tone, each of which may influence disease presentation and severity. Other environmental factors and modulators, such as ethnicity and geographical distribution need to be closely evaluated in assessing causality, and in establishing the specific diagnosis of the rhythm disorder. This can be facilitated not only by monitoring specific cardiac markers, but also by close observation of the pharmacological responses and the electrophysiological phenotypes and analysis of specific signaling pathways affected, i.e., mutations in ankyrin B protein that lead to altered Ca2+ signaling in adult cardiomyocytes resulting in premature ventricular beats as well as mutations in other signaling proteins, providing a significant rationale for dysrhythmia. The use of systems pharmacology linking drug targets, disease genes, and signaling protein interaction networks may allow individualization of therapy, which is particularly critical in establishing drug dosages and efficacy in children and aging patients with dysrhythmias and structural heart defects, a population for which pharmacokinetics has proven to be poorly defined and often unpredictable.

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Marín-García, J. (2011). Dysrhythmias/Channelopathies and Signaling Pathways. In: Signaling in the Heart. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9461-5_17

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