Excitation-contraction Excitation-contraction couplingcoupling

Sliding filament mechanism• independent studies by Huxley and

Huxley (no relation) in 1954

Excitation-ContractionExcitation-Contraction

contraction occurs when contraction occurs when CaCa2+2+ binds with troponin C binds with troponin Ceach cycle takes ~50 msec each cycle takes ~50 msec and sarcomere shortens and sarcomere shortens ~10 nm~10 nmcontraction ceases when contraction ceases when CaCa2+2+ is removed from is removed from sarcoplasmsarcoplasm

ATP Hydrolysis: OverviewATP Hydrolysis: Overview

in resting state, ATP is partially hydrolyzedin resting state, ATP is partially hydrolyzedmyosin head binds to actin filament when binding myosin head binds to actin filament when binding becomes availablebecomes availableATP is completely hydrolyzed, and Pi and ADP ATP is completely hydrolyzed, and Pi and ADP are released from myosin headare released from myosin headactomyosin complex is broken when ATP binds actomyosin complex is broken when ATP binds to myosinto myosin

Maintenance of [ATP]Maintenance of [ATP] ii

myosin ATPasemyosin ATPase

ATP + HATP + H22O <O <—————> —————> ADP + Pi + H ADP + Pi + H++

creatine kinasecreatine kinase

PCr + ADP + HPCr + ADP + H++ < <—————> —————> Cr + ATP Cr + ATP

adenylate kinaseadenylate kinase

ADP + ADP <ADP + ADP <—————> —————> ATP + AMP ATP + AMP

ATP Hydrolysis: ATP Hydrolysis: WeakWeak Binding Phase Binding Phase

Transition 1Transition 1 – A-M binding; ATP enters myosin ATP pocket – A-M binding; ATP enters myosin ATP pocketTransition 2Transition 2 – ATP weakens A-M complex, myosin detaches – ATP weakens A-M complex, myosin detachesTransition 3Transition 3 – ATP partially hydrolyzed – ATP partially hydrolyzedTransition 4Transition 4 – myosin weakly reattaches to next actin molecule – myosin weakly reattaches to next actin molecule

ATP Hydrolysis: ATP Hydrolysis: StrongStrong Binding Phase Binding Phase

Transition 5Transition 5 – Pi released from myosin ATP pocket; myosin – Pi released from myosin ATP pocket; myosin cleft closes, strengthens bindingcleft closes, strengthens bindingTransition 6 Transition 6 – power stroke of myosin head– power stroke of myosin headTransition 7Transition 7 – ADP released (rate-limiting step) – ADP released (rate-limiting step)

Transition 1

Transition 2

Transition 3

Transition 5

Transitions 6-7Weak Binding

Strong Binding