Scheme 1

Illustration of the types of calcium-ion (Ca²⁺) channels in cells, including voltage-gated calcium channels, ligand-gated calcium channels (e.g., cAMP-modulated Ca²⁺ channels), inositol-1,4,5-triphosphate receptor (IP₃R)-modulated Ca²⁺ channels, and RyR-modulated Ca²⁺ channels (CICR process). CICR is typically a positive-feedback system. First, voltage-gated Ca²⁺ channels are activated to allow a small amount of Ca²⁺ to pass through the cell membrane. Ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) are sensitive to the above Ca²⁺ influx and open the nanochannels, which cause a large amount of Ca²⁺ stored in the SR to be released into the cytosol. A remarkable increase in cytosolic Ca²⁺ activates muscle contraction. Adapted with permission²