1. Contraction Mechanism Actin and myosin interact via to the sliding filament mechanism Resting State –Actin bound by caldesmon –Myosin light chain (MLC) dephosphorylated –Intracellular [Ca 2+ ] low Rise in intracellular Ca 2+ triggers contraction Ca 2+ enters from the extracellular space (some from SR) Increase in [Ca 2+ ] caused by: –Excitation by neurotransmitters (extracellular Ca) –Hormonal signaling via receptors & 2 nd messengers (SR Ca) –Ca flux can be inhibited by various inhibitory stimuli – hormonal & neuronal

2. Regulation of SM Contraction Actin

3. Role of Ca 2+ for Contraction Ca 2+ binds to calmodulin (Cam) Ca-Cam binds to & activates myosin light chain kinase (MLCK) Ca-Cam binds to & inactivates caldesmon Active caldesmon binds actin Ca-Cam-inactivated caldesmon can’t bind actin The free actin is available for myosin to bind Activated MLCK phosphorylates myosin head region allowing cross bridges with actin to form