C2006/F2402 '06 Outline for Lecture 20 -- (c) 2006 D. Mowshowitz -- Lecture updated 04/11/06
Useful Web Sites & Animations
Handouts (not on web): 20A (muscle structure) & 20B (cross bridge cycle);
20 C (smooth muscle & pacemaker potentials) & 20D (comparisons between types of
muscles). A & B are very
similar to pictures in your texts. (C & D are from more advanced texts.)
Extra copies are available in
boxes on 7th floor Mudd.
I. Muscle
A. Three main types -- smooth, cardiac and skeletal (See handout 20 A or Purves 47.1 (47.5) or Becker Chap. 16 (23). Compare Becker figs. 16-10, 16-22 & 16-23 (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. 16-16 [23-16].)
3. Electrically excitable
C. Some Major Differences
→ open/shut K+ leak channels, Ca++ channels and/or the If channels → faster or slower depolarization = steeper or flatter pacemaker potential → pacemaker cells fire AP sooner or later → faster or lower heartbeat. (see Purves 49.6 (49.7))1. Cells Fused? Single cells (smooth) vs fused at ends (cardiac) vs fused, multinucleate (skeletal)
2. Striated vs. not.
3. Role of ATP. Is ATP needed to maintain contraction?4. Pacemaker activity or not? (cardiac always does; some smooth muscle does). See handout 20C. What is pacemaker activity?
a. Pacemaker Potential: Cell membrane gradually depolarizes without any external stimulus. (No stable RMP.) Depolarization = pacemaker potential.
b. It's a Cycle: When depolarization reaches threshold, cell fires an AP. Membrane then hyperpolarizes, and depolarization starts again.
c. Channels: Spontaneous depolarization caused by opening of Na+/K+ channels (called If channels) and/or closing of K+ channels. (Ca++ channels involved at late stages.)
d. Autonomic NS effects -- can effect opening/closing of channels and thereby change timing of pacemaker.
Example (in heart): S/PS release transmitters
5. Control of bridge cycle -- all use Ca++, but details differ, as explained in detail below.
a. What protein binds Ca++? Calmodulin or troponin?
b. What protein is altered to allow contraction -- actin or myosin?
c. When actin or myosin is altered, what is nature of change? Change in conformation or in state of phosphorylation?
d. Where does the Ca++ come from? Extracellular or ER?
6. What controls contraction? (If there is no pacemaker)
a. Skeletal Muscle
(1). Innervated by somatic system
(2). Signal is always excitatory.
(3). Neurotransmitters at nerve/muscle synapse use nicotinic (direct -- ionotropic) receptors.
(4). Stimulus generates an AP in the muscle membrane, which causes release of Ca++.
b. Smooth Muscle
(1). Innervated by autonomic neurons (& affected by hormones).
(2). Stimulus can be excitatory or inhibitory.
(a). Hormones and autonomic neurotransmitters from postganglionic neurons affect channels & pumps indirectly using 2nd messengers. (Use indirect, metabotropic receptors.)
(b). 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.
(3). Stimulus can generate an action potential (to open Ca++ channels) or act through a second messenger to affect Ca++ levels (w/o going through an AP). See examples above.
D. Details of skeletal muscle structure & overview of how filaments slide-- see handout 20A or Purves fig. 47.3 (47.7) or Becker Ch. 16, fig. 10-15 (Chap 23, same figures).
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. See handout 20D for reference.
II. 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 16-18 (23-18); Purves 47.6 (47.10 -- this includes role of Ca++ as well as ATP). Cycle can start anywhere, but description below assumes you start with state B on handout and carry out step 1 first. Role of Ca++ is omitted in this go round.
→ state C)1. ADP-myosin binds to actin -- Pi released ( converting 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 20B or Purves 47.4 (47.8) or Becker 16-19 (23-19)
1. Structure: Tropomyosin and troponin are part of the thin filaments
2. Tropomyosin role -- blocks myosin binding sites on actin
3. Ca++ binds to troponin (not tropomyosin)
4. Effect of Ca++ binding -- 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. 16-20 & 21 (23-20 & 21) or Purves 47.5 (47.9)
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 EPSP 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. 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 (SR = sarcoplasmic reticulum = ER of muscle cell) → 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.)
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 47.7 (47.11)
→ fully contracted muscle that stays contracted = tetanus (requires continual splitting of ATP to maintain contraction).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
E. Types of skeletal muscle fibers and contractions -- See Purves 47.8 (47.12). This section (E) is included FYI only.
1. Muscle can be fast twitch or slow
| Fast Twitch | Slow Twitch | |
| ATPase of Myosin | Higher | Lower |
| Speed of Bridge Cycle | Faster | Slower |
| Reach max. tension (after EPP) | Rel. quickly | Rel. slowly |
| Size/ max. possible tension | Usually larger | Usually smaller |
| Overal Properties of Muscle | "flash in the pan" | "slow but steady" |
| Used for | quicker response, bursts of activity (sprinters) |
slower response, sustained activity (long distance runners) |
2. Muscle can be oxidative or glycolytic
| Glycolytic | Oxidative | |
| Color | paler ("white meat") | Red color due to myoglobin to store oxygen ("red meat") |
| # of capillaries to deliver oxygen | Rel. low | Relatively high |
| # of mitochondria for oxidative metabolism | Rel. low | Relatively high |
| Need for oxygen | Low | High. Need more oxygen but less glucose -- "Oxygen dependent" but energy metabolism is more efficient |
| Ease of Fatigue | rel. quickly | relatively slowly -- Does not accumulate lactic acid |
| Glycolytic enzymes | Higher | Lower |
3. Fast/slow vs glycolytic/oxidative: Usually Fast twitch fibers are glycolytic; fatigue easily etc.; Slow twitch fibers are oxidative. Some muscle fibers are fast but oxidative.
4. Effect of 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
A. What use is smooth muscle? What unique properties does it have?
1. Location -- much of it makes up walls of hollow organs & tubes. Maintains shape and pushes contents along.
2. Contraction speed & rate of fatigue -- relatively slow for both.
3. Latch state possible -- can remain contracted for prolonged period without input of ATP. (One ATP split per bridge cycle, but cycle is much slower.)
4. Length over which it contracts/stretches -- relatively long.
5. Contracts/relaxes in response to many different stimuli -- nerves, hormones, stretch, etc.
Overall: Can integrate multiple signals and maintain "tone" over wide range of length with economical use of ATP.
B. Structure
1. Smooth muscle contains no troponin (does have tropomyosin, but doesn't block actin-myosin binding sites)
2. Arrangement of actin/myosin bundles -- see handout 20A or 20C or this picture.
3. Intermediate filaments -- connect dense bodies & help hold bundles in place. (Dense body = same function as Z line in skeletal muscle.)
4. No T tubules.
5. Two Types.
a. Single Unit smooth muscle -- the cells are connected by gap junctions and contract as a unit.
b. Multi unit smooth muscle -- the cells are not coupled electrically; cells are stimulated and contract individually.
6. Structure of nerve/muscle synapse -- See handout 20C. 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.
C. How Ca++ triggers contraction
1. Role of Ca++: State of thick filaments, not state of thin, are affected by Ca++.
2. Where Ca++ comes from:a. Most Ca++ comes from outside of cell. Neurotransmitters, hormones etc. open Ca++ channels in plasma membrane using second messengers, and Ca++ comes in from extracellular fluid (ECF). In some smooth muscles, voltage gated Ca++ channels open and generate an AP.
b. A little Ca++ is released by the ER.
3. Ca++ binding protein: Calmodulin, not troponin, controls response to Ca++. See Becker fig. 16-24 (23-24) & handout 20C.
a. Calmodulin-Ca++ complex forms
b. Calmodulin--Ca++ complex binds to and activates a kinase (MLCK)
c. Kinase phosphorylates and activates myosin (so it can bind actin).
Next Time: wrap up of smooth muscle, & a little on cardiac muscle; then kidney function.
