Chapter 24 - Malignant hyperthermia syndrome and hydrogen sulfide signaling: Role of Kv7 channels

Abstract

Despite the genetic basis of malignant hyperthermia (MH) syndrome are well established, the diagnosis still needs an invasive procedure called In Vitro Contracture Test (IVCT). This strongly suggests that alternative/additive mechanisms are involved in the MH syndrome susceptibility. Recently, hydrogen sulfide (H2S) signaling has been evaluated as a new player in MH syndrome. Indeed, in MHS subjects there are local augmented levels of CBS-derived H2S within the skeletal muscle, not valuable in plasma. Being H2S molecular targets, Kv7 and KATP channels are involved in anomalous behavior observed in SKM of susceptible patients. Persulfidation has been demonstrated as the molecular mechanism through which H2S modifies Kv7 channels activity switching the hyperpolarizing response (resting condition) to depolarizing (contraction). Finally, the discovery of H2S signaling and potassium channel involvement in the MH appearance could help to better clarify the molecular basis of the syndrome and to define a new less invasive procedure for diagnosis.