Calcium Transport Mechanisms in Muscle Cells

Muscle function depends on the precise movement of calcium ions between cytosolic and intracellular stores. At rest, cytosolic Ca2+ is maintained at low nanomolar levels by active uptake into the sarcoplasmic reticulum (SR) via sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCAs) and by sequestration into other organelles. Upon depolarisation, rapid Ca2+ release through ryanodine receptors (RyRs) triggers contraction, after which SERCAs restore basal Ca2+ by pumping ions back into the SR using ATP hydrolysis. Additional pathways such as store-operated calcium entry (SOCE) and mitochondrial uptake cooperate to refill stores and shape cytosolic signals. Luminal buffer proteins within the SR modulate free Ca2+ and influence uptake and release kinetics. Regulatory peptides and post-translational modifications fine-tune pump activity in response to physiological demands. Disruption of these transport mechanisms underlies a range of pathologies from heart failure to skeletal muscle fatigue, making calcium handling a key target for therapeutic intervention.

Research from Nature Portfolio

Recent studies have revealed that phosphorylation of SERCA2 at a specific serine residue acts as a dynamic switch in cardiac Ca2+ homeostasis. Increased phosphorylation in ischaemic myocardium correlates with reduced pump efficiency and heightened susceptibility to cytosolic Ca2+ overload. Experimental prevention of this modification enhanced SERCA2 activity, protected against calcium-driven cell death in cardiomyocytes and mitigated infarct size in animal models. These findings refine our understanding of excitation–contraction coupling and underscore the therapeutic potential of modulating SERCA2 phosphorylation in acute myocardial injury.

Calcium Transport Mechanisms in Muscle Cells publication trend

The graph below shows the total number of articles in calcium transport mechanisms in muscle cells across all publications each year (not limited to Nature Index journals).

Technical terms

Excitation–contraction coupling: The process by which an electrical impulse across the muscle membrane triggers calcium release and subsequent contraction.

Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA): A P-type ATPase that uses ATP to transport Ca2+ from the cytosol into the SR lumen, facilitating muscle relaxation.

Sarcoplasmic reticulum (SR): A specialised intracellular membrane network in muscle cells that stores and releases Ca2+ to regulate contraction.

Ryanodine receptor (RyR): A calcium release channel on the SR membrane responsible for rapid efflux of Ca2+ into the cytosol to initiate contraction.

Store-operated calcium entry (SOCE): A mechanism by which depletion of SR Ca2+ triggers influx of extracellular Ca2+ through plasma-membrane channels to replenish stores.

Secretory pathway Ca2+-ATPase (SPCA): A Golgi-localised P-type ATPase that transports Ca2+ into the secretory pathway, supporting protein processing and ionic homeostasis.

References

1. Structure and transport mechanism of the human calcium pump SPCA1. Cell Research (2023).
2. SERCA2 phosphorylation at serine 663 is a key regulator of Ca2+ homeostasis in heart diseases. Nature Communications (2023).
3. Sarcoplasmic Reticulum Ca2+ Buffer Proteins: A Focus on the Yet-To-Be-Explored Role of Sarcalumenin in Skeletal Muscle Health and Disease. Cells (2023).
4. A bioelectrochemical approach based on a solid supported membrane to evaluate the effect of natural products on Ca2+-ATPase: The case of 6-gingerol. Electrochimica Acta (2023).