Physiology 11

Front 1

Skeletal Muscle Contraction

Back 1

When muscles shorten (contract):
-sarcomeres shorten
-^ amount of overlap between thick & thin filaments

Front 2

Sliding Filament Mechanism

Back 2

-In order for actin to move along myosin, there must be cyclical binding (cross-bridge formation) and releasing (cross-bridge release) of the linkage between actin and the myosin head.
-ATP required for cross-bridge (“x-bridge”) release.

Front 3

Sliding Filament Mechanism – Overview

Back 3

1. binding: myosin cross bridge binds to actin molecule

2. power stroke: cross bridge bends, pulling thin myofilament inward

3. detachment: cross bridge detatches at end of power stroke and returns to original conformation

4. binding: cross bridge binds to more distal actin molecule; cycle repeats

Front 4

OVERVIEW: EXCITATION-CONTRACTION COUPLING

Back 4

-Combination (coupling) of mechanical & electrical events in a muscle fiber

-Broken down into following steps
--ACh released from motor neuron
--End-plate potential generated  AP in muscle fiber
--AP triggers Ca+2 release from sarcoplasmic reticulum (SR)
--Ca+2 combines binds to troponin  contraction initiated

Front 5

Excitation-contraction coupling: steps 1 - 2

Back 5

-ACh release from motor neuron
-End-plate potential generated in muscle cell PM
-AP initiated and travels across PM, down T-tubules

Front 6

Excitation-contraction coupling: step 2 (cont’d.)

Back 6

-APs in T-tubules trigger opening of voltage-gated Ca+2 (release) channels in sarcoplasmic reticulum (SR)…

-Close association of T-tubules, SR, & myofibrils

Front 7

Ca+2 release from SR

Back 7

AP’s traveling down t-tubules activates
-DHP (dihydropyridine) is voltage-gated Ca+2 channel in muscle PM (t-tubule)
-Ry (ryanodine) is Ca+2 release channel in SR mechanically gated to DHP

Front 8

Excitation-Contraction Coupling: Step 3

Back 8

-Ca+2 enters into sarcoplasm down its concentration gradient
-Ca+2 binds to troponin C (TnC) on thin (actin) filaments

Front 9

Step 4: Ca+2 Binding

Back 9

Ca+2 binds to troponin (TnC)  tropomyosin-troponin complex moves to expose myosin binding sites on actin

Front 10

Step 5: Cross-bridge Formation

Back 10

Myosin head attaches to actin -> x-bridge formed

Front 11

Step 6: Thin Filament Slides Toward Center of Sarcomere

Back 11

Cross-bridge formation triggers power stroke  actin slides over myosin toward center of sarcomere

Front 12

The Power Stroke

Back 12

-Binding of myosin to actin causes release of ADP & Pi from myosin head  release of nrg that causes myosin head to rotate, thereby pulling thin filament (toward center of sarcomere) past thick filament
-Actual step that requires nrg (new ATP) is the breakage of the x-bridge

Front 13

Step 7: Cross-bridge Release

Back 13

-After power stroke, x-bridge released when new ATP molecule binds onto myosin head (ATPase site)
-As long as Ca+2 present, cross-bridge cycling continues

Front 14

Step 8: Relaxation Phase

Back 14

-AP’s stop, so ACh no longer released.
-ACh dissociates from nicotinic receptors, and AChE does its job.
-SR Ca+2 channels close.

Front 15

Step 8: Relaxation Phase (cont’d.)

Back 15

-Active transport pumps (= calsequestrin) pump Ca+2 back into SR, incl. Ca+2 released from TnC
-Cycle begins again

-Tropomyosin moves back into its blocking position of myosin binding sites on actin

Front 16

steps of cross bridge formation

Back 16

Excitation-contraction coupling: steps 1 - 2

Ca+2 release from SR

Excitation-Contraction Coupling: Step 3

Step 4: Ca+2 Binding

Step 5: Cross-bridge Formation

Step 6: Thin Filament Slides Toward Center of Sarcomere

Step 7: Cross-bridge Release

Step 8: Relaxation Phase (cont’d.)

Front 17

Importance of Ca+2 for Contraction

Back 17

-ATP needed for x-bridge release, but intracellular Ca+2 levels control x-bridge formation during contraction
-Normally, [Ca+2]ICF < 10-8 M, but when [Ca+2]ICF > 10-7 M, x-bridge formation triggered
-As long as Ca+2 present, binding sites available for x-bridge formation
-Force generated by muscle fiber ^ with ^ [Ca+2]ICF