Local calcium dynamics and signalling in cardiomyocytes.

Area of Science:

• Cardiology
• Cellular Physiology
• Molecular Biology

Background:

• Calcium (Ca²⁺) signalling is vital for cardiomyocyte function, impacting excitation-contraction, excitation-transcription, and excitation-bioenergetics coupling.
• Ca²⁺ microdomains compartmentalize signalling, ensuring efficient cardiac function.
• Dysfunctional Ca²⁺ handling and dyadic remodelling are implicated in heart failure and arrhythmias.

Purpose of the Study:

• To review the organization and functional importance of Ca²⁺ microdomains in cardiomyocytes.
• To explore pathological alterations in Ca²⁺ microdomains during heart failure.
• To discuss therapeutic strategies targeting Ca²⁺ signalling mechanisms.

Main Methods:

• Review of existing literature on Ca²⁺ signalling and microdomains in cardiac physiology and pathology.
• Analysis of the role of dyadic microdomains, L-type Ca²⁺ channels, and ryanodine receptor Ca²⁺-release channels (RYR2).
• Examination of nuclear Ca²⁺ roles in gene expression and pathological remodelling.

Main Results:

• Dyads, critical microdomains for excitation-contraction coupling, facilitate Ca²⁺-induced Ca²⁺ release.
• Heart failure involves dyadic remodelling and altered Ca²⁺ handling, leading to contractile dysfunction and arrhythmias.
• Ca²⁺ microdomains are dynamic and influenced by signalling pathways like β-adrenergic signalling, presenting therapeutic targets.

Conclusions:

• Ca²⁺ microdomains are crucial for normal cardiomyocyte function and their disruption drives heart failure pathology.
• Targeting Ca²⁺ microdomains and signalling offers potential therapeutic avenues for heart failure and arrhythmias.
• Further understanding of these dynamic microdomains is essential for developing effective cardiac treatments.