μ-calpain and calpain-3 are activated by elevations in [Ca2+] in the physiological range of 2-20 μM [Ca2+]free in skeletal muscle (Murphy et al., 2006). Adult Long Evans hooded rats were killed by an overdose of halothane, as approved by the Animal Ethics Committee at La Trobe University, and the extensor digitorum longus (EDL) muscles were removed. Various properties of μ-calpain and calpain-3 in segments of single muscle fibres from rat skeletal muscle were investigated to address the question of how calpains might be regulated to deal with the frequent episodes of very high intracellular [Ca2+] experienced in skeletal muscle. μ-calpain is mostly diffusible in a fibre at resting [Ca2+] but rapidly binds at higher [Ca2+]. It shows relatively low proteolytic activity and little autolysis if exposed to ≤ 2 μM Ca2+ for minutes. However if [Ca2+] reaches higher levels (5 to 20 μM) some μ-calpain becomes autolyzed and remains proteolytically active even at ∼300 nM Ca2+, only de-activating if [Ca2+] falls to ∼50 nM. This chronic activation effect will be particularly deleterious if resting [Ca2+] is elevated in the cytoplasm or under the sarcolemma, as in muscular dystrophy and after eccentric contractions.
Murphy RM, Snow RJ & Lamb GD (2006) American Journal of Physiology (Cell Physiology), 290: C116-122.