It has previously been shown that excitation is associated with an uptake of Ca²⁺ in rat skeletal muscle (3). The mechanism behind this uptake has remained elusive. Store-operated Ca²⁺ entry (SOCE) or excitation coupled Ca²⁺ entry (ECCE) may serve as possible entry mechanisms. The molecular basis for SOCE has now been elucidated and involves the Ca²⁺ sensing protein STIM1 in the SR membrane and the pore forming Orai in the cellular membrane (4). ECCE seems to involve the ryanodine receptors (RyR) in the SR membrane and the dihydropyrimidine receptors (DHPR) in the cellular membrane. ECCE differs from SOCE that it does not require emptying of intracellular Ca²⁺ stores but depends on depolarization of the membrane (2). STIM1 haploinsufficiency has been shown to affect tetanic force in mice (5). Both SOCE and ECCE is blocked by SKF 96365 (1). The aim of this study was to investigate whether SOCE is important for the maintenance of contractile function in rat skeletal muscle and to investigate whether SOCE or ECCE is involved in the observed excitation-induced uptake of Ca²⁺. Isolated EDL muscle from 4-week old Wistar rats were mounted at fixed length on a muscle holder connected to a transducer. The muscles were incubated in buffer with 0 Ca²⁺ either at rest or stimulated at 1 Hz for 120 min (0.2 ms pulses, 24 V/cm). Following incubation the muscles were allowed to recover for 40 min in either Ca²⁺-free buffer or normal Krebs Ringer (NKR) containing 1.27 mM Ca²⁺. Maximum tetanic force was measured prior to incubation, immediately after incubation and at 20 and 40 min recovery (90 Hz, 0.5 sec). Mean values ± SD are given. Statistical difference between groups was ascertained using a t-test for non-paired observations. Stimulation in Ca²⁺ free buffer led to a 60% loss of tetanic force. If muscles were allowed to recover in Ca²⁺ free buffer no force recovery was observed, however if muscles recovered in NKR a complete force recovery was observed. The amount of Ca²⁺ taken up during recovery was measured using ⁴⁵Ca and corresponded to 132±5 nmol/Ca²⁺ g wet wt. (n=3). Addition of the cation channel blocker SKF 96365 reduced the uptake of Ca²⁺ by 60% (to 48±36 nmol/Ca²⁺ g wet wt., n=3, P<0.05) and prevented force recovery. Stimulation at 1 Hz for 120 min led to a marked uptake of ⁴⁵Ca in accordance with previous studies (3). SKF reduced this stimulation induced uptake. From this study it is concluded that SOCE can be observed in whole isolated muscles and that this uptake is important for the maintenance of contractile function. The effect of SKF 96365 on the stimulation induced uptake of Ca²⁺ suggest involvement of SOCE or ECCE.