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Ryanodine receptor activity and store‐operated Ca 2+ entry: Critical regulators of Ca 2+ content and function in skeletal muscle
Store‐operated Ca 2+ entry (SOCE) is critical to cell function. In skeletal muscle, SOCE has evolved alongside excitation–contraction coupling (EC coupling); as a result, it displays unique properties compared to SOCE in other cells. The plasma membrane of skeletal muscle is mostly internalized as t...
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| Published in: | The Journal of physiology 2023-10, Vol.601 (19), p.4183-4202 |
|---|---|
| Main Authors: | , , , , , |
| Format: | Article |
| Language: | English |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
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| Summary: | Store‐operated Ca
2+
entry (SOCE) is critical to cell function. In skeletal muscle, SOCE has evolved alongside excitation–contraction coupling (EC coupling); as a result, it displays unique properties compared to SOCE in other cells. The plasma membrane of skeletal muscle is mostly internalized as the tubular system, with the tubules meeting the sarcoplasmic reticulum (SR) terminal cisternae, forming junctions where the proteins that regulate EC coupling and SOCE are positioned. In this review, we describe the properties and roles of SOCE based on direct measurements of Ca
2+
influx during SR Ca
2+
release and leak. SOCE is activated immediately and locally as the [Ca
2+
] of the junctional SR terminal cisternae ([Ca
2+
]
jSR
) depletes. [Ca
2+
]
jSR
changes rapidly and steeply with increasing activity of the SR ryanodine receptor isoform 1 (RyR1). The high fidelity of [Ca
2+
]
jSR
with RyR1 activity probably depends on the SR Ca
2+
‐buffer calsequestrin that is located immediately behind RyR1 inside the SR. This arrangement provides in‐phase activation and deactivation of SOCE with a large dynamic range, allowing precise grading of SOCE flux. The in‐phase activation of SOCE as the SR partially depletes traps Ca
2+
in the cytoplasm, preventing net Ca
2+
loss. Mild presentation of RyR1 leak can occur under physiological conditions, providing fibre Ca
2+
redistribution without changing fibre Ca
2+
content. This condition preserves normal contractile function at the same time as increasing basal metabolic rate. However, higher RyR1 leak drives excess cytoplasmic and mitochondrial Ca
2+
load, setting a deleterious intracellular environment that compromises the function of the skeletal muscle.
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| ISSN: | 0022-3751 1469-7793 |
| DOI: | 10.1113/JP279512 |