It was established decades ago that excitation–contraction (EC) coupling relies on the depolarization-dependent release of stored calcium for skeletal muscle contraction and since that time considerable effort by many groups have detailed the molecular mechanism of calcium release underlying EC coupling (Edman & Grieve, 1964; Caputo & Gimenez, 1967; Luttgau & Oetliker, 1968). More recently, growing evidence suggests that alternative calcium signalling pathways exist in skeletal muscles that rely on calcium entry (Hopf et al. 1996; Kurebayashi & Ogawa, 2001). In this symposium, RT Dirksen provided an important overview of calcium entry in skeletal muscle (Dirksen, 2009). Two forms of Ca2+ entry have been characterized in skeletal muscle fibres: excitation-coupled calcium entry (ECCE) and store-operated calcium entry (SOCE)(Williams & Rosenberg, 2002; Cherednichenko et al. 2004). ECCE is activated in muscle cells following prolonged membrane depolarization that is independent of the calcium stores. ECCE requires functioning L-type calcium channel (LTCC) and ryanodine receptor (RYR1) channels, but the molecular identity of the pore remains undefined although it is likely to involve the LTCC (Hurne et al. 2005; Bannister et al. 2008, 2009).

ECCE is altered in malignant hyperthermia (MH) and may contribute to the disordered calcium signalling found in muscle fibres of MH patients (Cherednichenko et al. 2008). SOCE on the other hand requires depletion of the internal stores and has been best characterized in non-excitable cells (Putney, 1986, 2007). SOCE in skeletal muscle was described some time ago in myotubes (Hopf et al. 1996), but it was not until the discovery of two important molecules, stromal interaction molecule 1 (STIM1) and Orai1 in non-excitable cells, that the importance of