Figure 1

Effects of MH triggers on Ca²⁺release. A: Uncontrolled myoplasmic Ca²⁺ release is the key to malignant hyperthermia. The most prominent cytosolic Ca²⁺ elevation results from the freeing of stored sarcoplasmic Ca²⁺ mediated by ryanodine receptor type 1 (RyR1). While volatile anesthetics stimulate Ca²⁺ release via RyR1, succinylcholine acts indirectly by activating the nicotinergic acetylcholine receptor (nAChR), a nonspecific cation channel, resulting in continuous local depolarisation. The depolarization can trigger propagated action potentials and will further activate the dihydropyridine receptors (DHPR, Ca_V1.1) leading to the gating of both Ca²⁺ release from the SR via RyR1 and L-type Ca²⁺ current from the extracellular space. B: Heavy SR from rat muscle was maximally preloaded with Ca²⁺ before testing the potential Ca²⁺ releasing agonists halothane, isoflurane, enflurane and succinylcholine. The resulting Ca²⁺ release is via the RyR1 channel. Halothane, isoflurane and enflurane induced Ca²⁺ release from the SR vesicles but succinylcholine had no detectable effect. Results are expressed as mean ± standard error from six separate SR specimens. Of the three anesthetics tested, halothane showed the greatest potency and efficacy.* C: Succinylcholine (SCh) significantly increases halothane induced contractures in malignant hyperthermia susceptible individuals. However, SCh alone does not lead to the development of pathological contractures in MHN or MHS individuals*. *Part of the data from Figure 1B and C was published in Klingler et al. in 2005 [25].