Calcium entry triggers calcium release from the sarcoplasmic reticulum
Mnemonic
“Depolarise, release calcium, slide, and pump it back”:
- Action potential travels down the T tubule
- Dihydropyridine receptor senses the voltage change
- Ryanodine receptor on the sarcoplasmic reticulum opens, releasing calcium
- Calcium binds troponin C, moving tropomyosin off the actin binding site
- Cross bridges form and the filaments slide, consuming ATP
- SERCA pumps calcium back into the sarcoplasmic reticulum, again using ATP
“ATP is needed to relax, not just to contract”, which is why rigor mortis occurs when ATP runs out and why ischaemic muscle becomes stiff.
Cardiac muscle differs in one crucial way: it requires calcium induced calcium release, so extracellular calcium entering through L-type channels triggers the sarcoplasmic release. Skeletal muscle does not, because the two receptors are physically coupled.
That difference is why calcium channel blockers reduce cardiac contractility but not skeletal muscle strength, and why the heart is so dependent on extracellular calcium.
Expansion
- Action potential spreads along the sarcolemma and into the T tubules
- L-type calcium channels open in phase 2, admitting a small amount of calcium
- That calcium triggers the ryanodine receptors of the sarcoplasmic reticulum to release a much larger store: calcium-induced calcium release
- Calcium binds troponin C, moving tropomyosin off the actin binding sites
- Cross-bridge cycling produces contraction
- Relaxation follows as calcium is pumped back by SERCA and extruded by the sodium-calcium exchanger
The dependence on trigger calcium from outside the cell is the key difference from skeletal muscle, and it explains two drug effects: calcium channel blockers reduce the trigger, while digoxin inhibits the sodium-potassium ATPase, raising intracellular sodium, which slows the sodium-calcium exchanger and leaves more calcium inside.