1.

Compare the smooth and cardiac muscles with the skeletal muscles with regards to the following:
Sources of activating Ca, site of calcium regulation, speed of contraction.
a. Skeletal muscle
Source of activating Ca - released from terminal cisternae of Sarcoplasmic reticulum via
opening of Ryanodine channels
**When an action potential is transmitted along the sarcolemma of the muscle fiber and then
down the T tubules, Ca++ is released from the terminal cisternae SR into the myoplasm. This
release of Ca++ from the SR raises intracellular [Ca++], which in turn promotes actin-myosin
interaction and contraction. The action potential is extremely
short-lived (5 msec). The elevation in intracellular [Ca++] begins slightly after the action
potential and peaks at approximately 20 msec. This increase in intracellular [Ca++] initiates a
contraction called a twitch.
***skeletal muscle contractions are neurogenic as they require synaptic input from motor
neurons to produce muscle contractions. A single motor neuron is able to innervate multiple
muscle fibers, thereby causing the fibers to contract at the same time. Once innervated, the
protein filaments within each skeletal muscle fiber slide past each other to produce a contraction,
which is explained by the sliding filament theory
Site of calcium regulation troponin C
***Ca++ promotes this increase in tension is as follows. Ca++ released from the SR binds to
troponin C. Once bound with Ca++, troponin C facilitates movement of the associated
tropomyosin molecule toward the cleft of the actin fi lament. This movement of tropomyosin
exposes the myosin binding site on the actin fi lament and allows a cross-bridge to form and
thereby generate tension (see later). Troponin C has four Ca++ binding sites. Two of these sites
have high affi nity for Ca++ but also bind Mg++ at rest. These sites seem to be involved in
controlling and enhancing the interaction between the troponin I and troponin T subunits. Once
myosin and actin have bound, ATP-dependent conformational changes in the myosin molecule
result in movement of the actin fi laments toward the center of the sarcomere. Such movement
shortens the length of the sarcomere and thereby contracts the muscle fi ber. The mechanism by
which myosin produces force and shortens the sarcomere is thought to involve four basic steps
that are collectively termed the crossbridge cycle

Speed of contr action; Skeletal muscles can be composed of fast-contracting fibers, slowcontracting fibers or a mixture of both.

b. Smooth muscle
Source of activating calcium: calcium sequestered in the S.R. of the smooth muscle cell. extracellular
calcium that can enter the smooth muscle cell via calcium channels on the membrane of the smooth muscle
cell.
****smooth muscle uses second messenger systems to open the calcium channels on the S.R. Receptors on
the smooth muscle membrane for such ligands as endothelin (released as a paracrine agent), Epinephrine
(released as a hormone or a neurotransmitter), and Ach (released as a neurotransmitter) connect to the Gq
protein and lead to the production of inosital triphosphate (IP3). The IP3 is then directly responsible for
opening the calcium channels on the S.R. membrane, allowing the calcium to enter the cytoplasm of the cell.
There is one important consequence of this process: Unlike skeletal muscle, smooth muscle can be made to
contract in the absence of an action potential.
**** both ligand-gated calcium channels and voltage-gated calcium channels present on the smooth muscle
membrane.
Site: calmodulin
***four Ca++ ions bind to the calmodulin, the Ca-calmodulin complex binds to the myosin light chain kinase
and activates it. Myosin light chain kinase (MLCK) is an enzyme that phosphorylates one of the two myosin
light chains associated with the myosin head. The MLCK hydrolyzes ATP and takes the inorganic phosphate
(Pi) from the ATP and puts it on the myosin light chain. Once the myosin light chain is phosphorylated, the
myosin head (probably because of the conformational change produced by phosphorylation) develops a high
affinity for the actin active site and binds readily to it

 Speed of contraction; Contract slowly and rhythmically.

***Smooth muscle contraction is much slower than that of skeletal muscle. This may be due to slow diffusion of Ca+
+ from outside the cell or to the slow rate of ATP hydrolysis or both. smooth muscle uses less energy to generate a
given amount of force, and it can maintain its force for long periods

b. Cardiac muscle
Source; much of the calcium for contraction must come from extracellular sources; it comes
in during the action potential.
***calcium-induced calcium release - influx of calcium from the ECF then triggers calcium release from the
sarcoplasmic reticulum;

Site; troponin
*** Calcium in the cytoplasm then binds to cardiac troponin-C, which moves the troponin complex
away from the actin binding site. This removal of the troponin complex frees the actin to be bound by
myosin and initiates contraction.

Speed; Intermediate speed of contraction yet contraction spreads quickly through

tissue due to intercalated discs
***Heart muscle exhibits many structural and functional characteristics
intermediate between those of skeletal and smooth muscle. Like skeletal muscle,
cardiac muscle contractions are strong, and utilise a great deal of energy. Like
some smooth muscle, cardiac muscle can contract without nervous stimulation
(i.e. it is myogenic)

2. Distinguish the similarities and differences between the contractile activities of smooth, cardiac and
skeletal muscles in relation to the increase in the cytosolic Ca++

3. Discuss the similarities or differences between the length-tension relationship of cardiac and skeletal
muscles

4. Discuss smooth muscle cross bridge cycling and explain why it can develop and maintain force with a
much lower rate of ATP hydrolysis. Discuss latch bridge mechanism.