Cross bridge Cycling in striated muscle

How do the thin filaments slide past the thick filaments?

• Cross bridge cycling
  - series of steps that result in active contraction in muscle that can lead to the generation of force and the shortening of muscle length

What is a cross bridge?

• the myosin molecule forming a bond with the myosin bonding site on the actin molecule in the thin filament

• bridge refers to connecting the thick and the thin filaments

• the number of cross bridges that are formed during contraction determines to a great extent the amount of force produced during contraction
  - the more cross bridges, the more force

Before the Bridge

• before the first step of the cross bridge cycle:
  1. the myosin binding sites on the actin molecules are exposed
  - meaning troponin has pulled topomyosin away from the actin site and allows for myosin to bind and form a cross bridge

• major shapes in myosin: sometimes referred to as cocked and uncocked or positions of high energy (cocked) or low energy (uncocked)

Step 1:

• myosin forms a bond and myosin is in a position of high energy (cocked)

• associated with the head of the myosin there is molecule of ADP and molecule of inorganic phosphate, referred to as pi
  - ADP and Pi are the products from the hydrolysis of the ATP molecule which is dead by the myosin head (the head is an enzyme)

• Pi falls off as a result of myosin binding to the act, causing a sublte shape change

Step 2: powerstroke

• myosin goes through a big conformational shape change
  - it goes from a position of high energy (cocked) to low energy (uncocked)

• this phase is called the powerstroke because this is the phase of cross bridge cycling where shortening takes place

• when the myosin goes from the cocked to the uncocked position, we pull the thin filaments towards the center of the sarcomere

• myosin has another subtle shape change and the ADP is realesed
  - myosin is still in uncocked position and is still bound to the actin

Step 3

• bring ATP in which binds to the ATP binding site on the myosin head which causes another subtle change in the shape of myosin

• the myosin detaches from the thin filament

Step 4

• the myosin breaks ATP down via hydrolysis to ADP and Pi

• the myosin gets recocked and if the myosin binding site on actin is still exposed, we can now form a new cross bridge

how can the cross bridge cycle be repeated?

1. if we have ATP
   - without ATP this stops

2. the myosin binding site on actin has to be exposed in order to produce a cross bridge which requires the ion calcium