C2006/F2402 '04 Outline for Lecture 20 --  (c) 2004 D. Mowshowitz  -- Lecture updated 04/13/04

Useful Web Sites & Animations

Handouts: 20A (muscle structure) & B (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.

1. Sensors Purves has a whole chapter on Sensory Systems. (Chapter # depends on which edition of the text you have.) We will go over the overall principles that are covered in the first few pp of the chapter, and a few details of specific detection systems. We will not cover all the details of each system. 

    A. Two types of Receptor Cells = sensory cells = special cells with molecular receptors for detecting stimuli

1. Modified neuron capable of generating AP itself

2. Cell that cannot generated an AP itself, but releases transmitter and triggers AP in next cell.

Question to ask yourself: What type of channels does a cell need in order to generate an AP?

    B. Receptor Proteins.

1. Special cells contain receptor proteins for stimuli (pressure, light, heat, chemicals, etc.).

2. How do protein receptors detect stimuli?

a. Stimuli --> Change in conformation of receptor --> open channels in membrane --> change in polarization of membrane.

b. How are channels opened? See Purves 45.1(42.1)

(1) Directly  -- receptor is a channel. (Examples: receptors for pressure, temperature, voltage)

(2) Indirectly -- through 2nd messengers (Examples: chemoreceptors, photoreceptors).

    C.  Graded (Receptor) Potentials.

1. Response to stimulus is graded. Stimulus --> local graded response. The more stimulus, the more channels open, and the bigger the graded potential.

2. Terminology

1. receptor potential -- graded response in receptor cell (cell which receives stimuli but does not generate its own AP)

2. generator potential  -- graded response  in modified neuron (cell which generates an AP)

    D. How Does Graded response generate an AP?  -- see Purves 45.2.(42.2) for the two methods.

1. In modified neuron. Graded response (generator potential) triggers AP in same cell (if stimulus.over threshold) --> input to CNS. Example: smell (olfaction).

Receptor --> G protein --> adenyl cyclase --> cAMP up --> open cation channel (cyclic nucleotide gated channel) --> depolarize cell --> AP. 

Question: Where will the action potential start? In what part of the cell? See Purves 45.3

2. In separate receptor cell: Graded response (receptor potential) triggers release/inhibition of transmitter by receptor cell -- amount of transmitter released proportional to stimulus. Transmitter generates IPSP or EPSP in neuron (next cell = post synaptic cell). Transmitter triggers AP in neuron if stimulus is over threshold --> input to CNS. Example: vision, taste.

Which type of receptor cell are you dealing with in problem 8-16?

3. Details for Vision -- see Purves 45.17 for signal transduction events.

a. Receptor cell (in the dark) releases an inhibitory transmitter, so post synaptic neuron remains hyperpolarized and does not fire.

Details FYI: Receptor cell is less polarized than usual to begin with; continually generates cGMP. This keeps cation channel open and cell partially depolarized --> release of neurotransmitter (inhibitory).

b. Binding of photons to pigment in receptor cell blocks release of inhibitory neurotransmitter. Post synaptic neuron depolarizes and fires an AP.

Details FYI: Receptor (rhodopsin  w/ cis retinal) binds photon --> rhodopsin w/ all trans retinal --> G protein --> activates phosphodiesterase (PDE) --> cGMP degraded --> cation channel closes, cell hyperpolarizes --> less (inhibitory) transmitter release --> AP in next cell. For more details see Purves Ch. 45 (42).

    E. All stimuli give same message to CNS (= AP's). If AP is all or nothing, how do you know which stimulus it was? And how much?

1. Number, frequency of AP's indicate length (duration) and strength (intensity) of stimulus.

2. Wiring (what part of brain is stimulated) indicates location of stimulus and type (modality) of stimulus  -- taste, stretch, etc. (Take a very sharp pencil and tap your upper lip. What sensors did you trip off?)

To review sensors, try Problem 8-16 . To review electrical communication overall, try 8-15.

II. Muscle

    A. Three main types -- smooth, cardiac and skeletal (See handout 20 A or Purves 47.5 (44.6) or Becker Chap. 23 (compare figs. 23-10, 23-22, 23-23).

    B. Common Features --

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

    C. Some Major Differences

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; smooth muscle does sometimes) .

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?

    D. Details of skeletal muscle structure & overview of how filaments slide-- see handout 20A or Purves fig. 47.7 (44.7) or Becker Ch. 23, fig 23-10 to 23-15.

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.

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

    A. Bridge Cycle -- How ATP is used to power sliding of thick and thin filaments -- steps (1 to 4) & states (A to E) match those on handout 20B. See also Becker 23-18; Purves 47.10 (44.10) -- this includes role of Ca++ as well as ATP. Cycle can start anywhere, but description below assumes you start with state B and carry out step 1 first. Role of Ca++ is omitted in this go round.

1. ADP-myosin binds to actin -- Pi 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 & Pi 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.

    B. Role of Ca++, troponin and tropomyosin (see handout B or Purves 47.8 (44.8) or Becker 23-19)

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.

    C. Where does Ca++ come from? How is it released? See Becker fig. 23-20 & 21 or Purves 47.9 (44.9)

1. Overall: Ca++ is released from SR (ER).

2. Presynaptic side: AP comes down motor neuron --> releases transmitter (AcCh)

3. Post synaptic side -- events at membrane/motor endplate:

a. AcCh binds to nicotinic receptors on motor endplate

b. Depolarization of muscle membrane = EPP (end plate potential)

c. One AP in neuron --> One EPP = sufficient depolarization to trigger AP in membrane of muscle fiber (One IPSP is not sufficient to trigger an AP in postsynaptic neuron.)

4. T tubules & SR

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

b. Changes in membrane potential in T tubule ---> signal to SR (ER) to release stored Ca++

(Coupling probably mechanical between protein/receptor/channel in T tubule membrane and channel in SR membrane)

Try problems 9-2 to 9-4.

   D. Twitches and Contractions

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 47.11 (44.11)

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)

    E. Types of skeletal muscle fibers and contractions -- See Purves 47.12.

1. Muscle can be fast twitch or slow

a. Speed/length of twitch depends on

(1) ATPase of myosin. High ATPase --> fast twitch (reach max. state of tension quickly) after EPP -- can run bridge cycle more quickly.

(2) Speed of Ca++ pump that puts Ca++ back into SR. Fast pump --> shorter twitch.

b. Fast twitch muscle properties (vs. Slow twitch)

(1). Relatively High ATPase

(2). Relatively fast Ca++ pump

(3). Usually glycolytic (vs oxidative)

(4). Reach max. tension relatively quickly

(5). Fatigue relatively rapidly

(6). Usually larger so develop higher max. tension

(7). Used for quick response, bursts of activity (vs. sustained activity)

2. Properties of oxidative fibers (vs glycolytic)

a. Red color due to myoglobin to store oxygen (vs pale)

b. Relatively high number of capillaries to deliver oxygen

c. Relatively high number of mitochondria to use the oxygen for oxidative metabolism

d. Need more oxygen but less glucose -- "Oxygen dependent" but energy metabolism is more efficient

e. Do not accumulate lactic acid -- a cause of fatigue

3. Exercise changes enzyme content and glycolytic/oxidative differences but not slow vs. fast or # fibers.

Question to think about: Most primates have 2 common types of muscle fibers -- glycolytic fibers with a high ATPase and oxidative fibers with a low ATPase, as described above. Some other organisms have a third type -- oxidative fibers with a high ATPase. What properties would you expect this third type of muscle to have? Compare it to the other two in terms of the features listed above. (The reasoning is what matters here, not the exact answers.)

IV. Smooth muscle

    A. Ca++ triggers contraction

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.

    B. Smooth muscle contains no troponin (does have tropomyosin)

    C. Calmodulin controls contraction/Ca++ response (instead of troponin). See Becker fig. 23-24.

1. Calmodulin-Ca++ complex forms

2. Calmodulin--Ca++ complex binds to and activates a kinase (MLCK)

3. Kinase phosphorylates and activates myosin (so it can bind actin)

    D. Actin accessibility may be regulated by other factors, but not Ca++

    E. Cross bridge Cycle -- Can maintain stable cross bridges without breaking ATP (bridge cycle is different)

    F. Speed -- contraction is slower than with skeletal, because:

1. A component requires phosphorylation before bridge cycle can begin

2. ATPase of myosin slower; get slower contraction (slower bridge cycle) but less fatigue

    G. Trigger for contraction

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

2. Structure of nerve/muscle synapse is different -- neurons have multiple varicosities (points of contact with smooth muscle), and muscle has no complex structure at synapse (no motor endplate). One autonomic neuron can stimulate multiple smooth muscle cells &/or multiple points on a single muscle cell.

Try problem 9-1, parts C & D, and try answering question 9-4 for the case of smooth muscle.  If we finish smooth muscle, you should be able to do all of the problems in set 9.

Next Time: cardiac muscle; heart structure & function; gas exchange.