Ca2+ sensitizers: An emerging class of agents for counterbalancing weakness in skeletal muscle diseases?
Ca(2+) ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca(2+) attachment, also known as Ca(2+) sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca(2+) sensitizers, are efficient agents to improve Ca(2+) sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca(2+) binding. Currently, such Ca(2+) sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness.
Ochala
Julien
J
Department of Clinical Neurophysiology, Uppsala University Hospital, Sweden. julien.ochala@neurofys.uu.se
D002118:Calcium / Q000819:agonists* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003285:Contractile Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use; D018908:Muscle Weakness / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009135:Muscular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D000077464:Simendan; D013829:Thiadiazines / Q000494:pharmacology / Q000627:therapeutic use
D002316:Cardiotonic Agents; D003285:Contractile Proteins; D006835:Hydrazones; D011724:Pyridazines; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D000077464:Simendan; D002118:Calcium