Impaired calcium release and reduced calcium transients in single muscle fibres of mouse with inactivation of calsequestrin-1 gene

Calsequestrin (CS) is the major Ca2+-binding protein in the sarcoplasmic reticulum (SR) with a dual role in excitation-contraction coupling: to buffer free Ca2+, thus increasing SR capacity, and to modulate the activity of the Ca2+ release channels. A mouse carrying a null mutation for the skeletal muscle isoform, or CS1 was generated. CS1-null mice were viable and fertile and their skeletal muscles are slightly atrophic but without signs of change in fibre type distribution. The maximal amount of calcium release was measured in single muscle fibres dissected from the of tibialis anterior and permeabilized with saponin and found to be reduced to less than 50% in CS1-null compared to WT animals. Calcium transients were recorded after loading fibres with fura-2. The amplitude of the transient induced by electrical stimulation was significantly lower in CS1-null compared to WT animals. Together the results indicate that CS-1 is important for the ability of the SR to accumulate and release suitable amounts of calcium.