Overview

The SR forms a network of longitudinal tubules over the A and I bands. At each A–I junction these tubules widen into paired terminal cisternae, which flank a T-tubule to form a triad. Inside, free Ca²⁺ is ≈0.5–1 mM, about ten thousand times the resting cytosolic level. Much more Ca²⁺ is held bound to the low-affinity, high-capacity protein calsequestrin.

Release: depolarisation of the T-tubule moves dihydropyridine receptors (DHPR, Caᵥ1.1), which are mechanically coupled to ryanodine receptors (RyR1) in the membrane of the terminal cisternae. RyR1 opens, and Ca²⁺ floods into the sarcoplasm within milliseconds. Reuptake: SERCA pumps (Ca²⁺-ATPase; SERCA1 in fast fibres, SERCA2a in slow and cardiac fibres) use ATP to move Ca²⁺ back into the SR, and the muscle relaxes. Relaxation is therefore an active, ATP-dependent process. In the heart, phospholamban regulates SERCA2a.

Parts & subdivisions

Terminal cisternae
Expanded ends next to the T-tubules. They contain RyR1 and calsequestrin.
Longitudinal (network) SR
Rich in SERCA pumps for Ca²⁺ reuptake.
Triad
One T-tubule between two terminal cisternae, at each A–I junction in mammalian skeletal muscle.

Function

Stores Ca²⁺ at rest
Releases Ca²⁺ to trigger contraction (excitation–contraction coupling)
Re-sequesters Ca²⁺ to bring about relaxation

Clinical significance

Malignant hyperthermia

An autosomal dominant pharmacogenetic disorder, usually caused by RYR1 mutations. Volatile anaesthetics or succinylcholine trigger uncontrolled Ca²⁺ release, causing rigidity, hypercarbia, tachycardia, hyperthermia, rhabdomyolysis and hyperkalaemia. Treatment is dantrolene, which blocks RyR1, plus stopping the trigger and active cooling.

Brody disease

Loss of SERCA1 function slows relaxation and causes exercise-induced stiffness and cramps.

Test yourself

In skeletal muscle, what directly opens the ryanodine receptor (RyR1) of the sarcoplasmic reticulum?

Ca²⁺ entering through L-type channels (Ca²⁺-induced Ca²⁺ release)
Mechanical coupling to voltage-sensing dihydropyridine receptors in the T-tubule
IP₃ generated by muscarinic receptors
cAMP-dependent phosphorylation by protein kinase A

Answer: Mechanical coupling to voltage-sensing dihydropyridine receptors in the T-tubule

In skeletal muscle, the DHPR (Caᵥ1.1) acts as a voltage sensor that is physically linked to RyR1, so depolarisation alone opens it. Ca²⁺-induced Ca²⁺ release through RyR2 is the mechanism in cardiac muscle.