C2006/F2402 '05 Outline for Lecture 21 --  (c) 2005 D. Mowshowitz  -- Lecture updated 04/19/05

Useful Web Sites & Animations

• Sliding filaments.  See diagram of sarcomere, with corresponding electron micrograph. (Go to pp.3 & 4)  By Michael Ferenczi.
• Sliding filaments. Animation of a sarcomere contracting, from electron microscope images, not drawings.  
• Actin-myosin crossbridge.  Watch the myosin head swivel, attaching and detaching from actin. From San Diego State University.
• Muscle structure and contraction

Handouts: 21A (muscle structure) & 21B (cross bridge cycle) -- not on web; very similar to pictures in texts. Extra copies will be available after class in boxes on 7th floor Mudd.

I. Muscle

1. Have actin MF and myosin

2. Actin and myosin slide past each other; neither shortens. (For skeletal muscle, see Becker fig. 23-16.)

3. Electrically excitable

1. Cells Fused? Single cells (smooth) vs fused at ends (cardiac) vs fused, multinucleate (skeletal)

2. Striated vs. not.

3. Role of ATP. Need ATP to remain contracted (skeletal) vs don't (smooth) vs never remain contracted (cardiac)

4. Pacemaker activity or not?  (cardiac always does; some smooth muscle does) .

5. Control of bridge cycle -- all use Ca⁺⁺, but details differ, as explained in detail below.

a. Use calmodulin or tropomyosin/troponin to control cross bridge formation?

b. Mask actin or myosin?

At this point, it helps to start making a table that summarizes all the similarities and differences between the 3 types of muscle. Fill it in as you go -- add to it as you find out more about the structure and function of the different types.

II. Skeletal Muscle Contraction  -- see animations listed at start of lecture.

1. ADP-myosin binds to actin -- P_i released ( converting state B --> state C)

2. Power stroke -- myosin, actin slide relative to one another. ADP released (converting state C --> state D).

3. ATP binds to myosin -- Myosin detaches from actin (converting state D --> state E = state A)

4. ATP is split -- form high energy form of myosin (ADP & P_i remain bound) -- Converting state A/E to state B.

5. Continue with step 1. Note ATP must continue to be split to maintain cross bridges and therefore tension in fiber.

1. Tropomyosin and troponin are part of the thin filaments

2. Tropomyosin blocks myosin binding sites on actin

3. Ca⁺⁺ binds to troponin (not tropomyosin)

4. Ca⁺⁺ binding to troponin --> movement of tropomyosin, exposing actin binding sites, so bridge cycle can go

5. How bridge cycle is blocked/regulated

a. In absence of Ca⁺⁺, bridge cycle is blocked at step 1 above.

b. In absence of ATP (& presence of Ca⁺⁺), cycle blocked at step 3 (rigor mortis).

Try problem 9-1, parts A, B & E, 9-11, and 9-12.

a. AP in muscle plasma membrane (sarcolemma) spreads to T tubules

b. AP in T tubule --> Ca⁺⁺ release from SR. Changes in membrane potential in T tubule ---> change in shape of protein in T tubule membrane --> opening of channels in SR (ER)  --> release of stored Ca⁺⁺

(Coupling probably mechanical between voltage sensitive protein in T tubule membrane and channel in SR membrane. The coupling system is similar, but not exactly the same, in smooth & cardiac muscle, as will be discussed.)

Try problems 9-2 to 9-4.

1. What's a twitch = 1 contraction = response to one EPP; measured by force exerted by muscle fiber when it contracts.

2. Twitches are summed. See Purves 47.7 (47.11)

a. Twitch lasts longer than muscle membrane AP

b. Second AP can trigger twitch before first is over --> more contraction (shortening)

c. Tetanus: Multiple AP's can ---> fully contracted muscle that stays contracted = tetanus (requires continual splitting of ATP to maintain contraction)

1. Muscle can be fast twitch or slow

2. Muscle can be oxidative or glycolytic

3. Usually Fast twitch fibers are glycolytic; fatigue easily etc.; Slow twitch fibers are oxidative.  Some muscle fibers are fast but oxidative.

4. Exercise changes enzyme content and glycolytic/oxidative differences but not slow vs. fast or # fibers. (Does change fiber size.) Slow and fast are innervated differently, and that can't be changed.

III. Smooth muscle

1. Role of Ca⁺⁺: State of thick filaments, not state of thin, are affected by Ca⁺⁺.

2. Where Ca⁺⁺ comes from: Most Ca⁺⁺ comes from outside of cell, not SR. AP opens voltage gated Ca⁺⁺ channels and Ca⁺⁺ comes in from extracellular fluid (ECF).

3. Ca⁺⁺ binding protein: Calmodulin, not troponin, controls response to Ca⁺⁺. Details of cycle next time.

    C. Regulation of contraction

1.  Autonomic system and/or hormones control contraction, not somatic system (as for skeletal).

a. Stimulus can be excitatory or inhibitory. Hormones and autonomic neurotransmitters from postganglionic neurons affect channels & pumps indirectly using 2nd messengers. (Compare to situation with nerve/muscle synapse.)

b. Stimulus can generate an action potential (which in turn affects Ca⁺⁺ channels) or act through a second messenger to affect Ca⁺⁺ levels (w/o going through an AP).  Examples in previous lectures: epinephrine can cause smooth muscle contraction (through IP3) or relaxation (through cAMP and Ca⁺⁺ pump). Response depends on receptors on smooth muscle.

c. Some smooth muscles have pacemaker cells that generate an AP spontaneously. Autonomic and/or hormonal stimulation modulate effects of internal signals from pacemakers.

2. Structure of nerve/muscle synapse is different -- neurons have multiple varicosities (points of contact with smooth muscle -- contain vesicles of neurotransmitter), and smooth muscle has no complex structure at synapse (no motor endplate). One smooth muscle cell (or group of cells) can get input from both PS and S. Details of structure next time.

Next Time: wrap up of smooth muscle, then cardiac muscle; heart structure & function; gas exchange.