Review Article

The Functional Role of Calcineurin in Hypertrophy, Regeneration, and Disorders of Skeletal Muscle

Table 1

Effect of calcineurin activation or inhibition on fiber growth (hypertrophy) of skeletal muscle in vivo.

ReferencesSpeciesExperimental systemModulating method of calcineurin activityOutcomes

Dunn et al. 1999 [51]MouseMechanical overloadingPharmacological inhibition for 4 weeks (CsA; 25 mg/Kg twice daily)Inhibition of fiber hypertrophy of the plantaris muscle

Bodine et al. 2001 [53]MouseMechanical overloadingPharmacological inhibition for 30 days (CsA; 15 mg/Kg once daily)No inhibition of fiber hypertrophy of the plantaris muscle

Sakuma et al. 2008 [59]MouseMechanical overloadingPharmacological inhibition for 2 weeks (CsA; 25 mg/Kg once daily)Inhibition of fiber hypertrophy of the soleus muscle

Parsons et al. 2003 [54]MouseGene-knock out (complete inactivation of cna 𝛼 or cna 𝛽 )Slow-twitch soleus muscle; hypertrophy (cna 𝛼 KO), atrophy (cna 𝛽 KO),
Several fast-twitch muscles (gastrocnemius, tibialis anterior, triceps brachii); no change (both cna 𝛼 and cna 𝛽 KO)

Talmadge et al. 2004 [56]MouseTransgenic manipulation (high-level expression of a constitutively active form of calcineurin)Slow-twitch soleus muscle; marked hypertrophy Several fast-twitch muscles (extensor digitorum longus, tibialis anterior, plantaris); no change

Oh et al. 2006 [58]Mouse(Transgenic manipulation (Flox-On approach), upregulation of calcineurin inhibitor (MCIP1))Atrophy of the soleus muscle

Mitchell et al. 2002 [60]MouseReloading after hindlimb suspensionPharmacological inhibition for 2 weeks (CsA; 12.5, 25, and 50 mg/Kg once daily)Inhibition of fiber growth (recovery) of both the soleus (25 and 50 mg/Kg) and plantaris (12.5, 25, and 50 mg/Kg) muscles

Miyazaki et al. 2006 [61]MouseReloading after hindlimb suspensionPharmacological inhibition for 4 weeks (FK506; 3–5 mg/Kg once daily)Inhibition of fiber growth (recovery) of the soleus muscle

Oishi et al. 2008 [62]RatReloading after hindlimb suspensionPharmacological inhibition for 2 weeks (CsA; 25 mg/Kg twice daily)Inhibition of fiber growth (recovery) of the soleus muscle