1. Excitation-contraction coupling Sliding filament mechanism independent studies by Huxley and Huxley (no relation) in 1954

2. Excitation-Contraction contraction occurs when Ca 2+ binds with troponin C each cycle takes ~50 msec and sarcomere shortens ~10 nm contraction ceases when Ca 2+ is removed from sarcoplasm

3. ATP Hydrolysis: Overview in resting state, ATP is partially hydrolyzed myosin head binds to actin filament when binding becomes available ATP is completely hydrolyzed, and Pi and ADP are released from myosin head actomyosin complex is broken when ATP binds to myosin

4. Maintenance of [ATP] i myosin ATPase ATP + H 2 O ADP + Pi + H + creatine kinase creatine kinase PCr + ADP + H + Cr + ATP adenylate kinase ADP + ADP ATP + AMP

5. ATP Hydrolysis: Weak Binding Phase Transition 1 – A-M binding; ATP enters myosin ATP pocket Transition 2 – ATP weakens A-M complex, myosin detaches Transition 3 – ATP partially hydrolyzed Transition 4 – myosin weakly reattaches to next actin molecule

6. ATP Hydrolysis: Strong Binding Phase Transition 5 – Pi released from myosin ATP pocket; myosin cleft closes, strengthens binding Transition 6 – power stroke of myosin head Transition 7 – ADP released (rate-limiting step)

7. Transition 1 Transition 2 Transition 3 Transition 5 Transitions 6-7 Weak Binding Strong Binding