6. Cardiac and Smooth Muscle

Question 1

Function of cardiac muscle

Answer 1

Pumps blood by contracting around a volume of blood which is then squeezed through the circulatory system.

Question 2

Structure of cardiac muscle

Answer 2

Myocardial cell dimater about 10um, length about 100um
Single nucleus, large number of mitochondria
Abundance of connective tissue around muscle
Extensive junctional connections

Question 3

Purpose of junction connections on cardiac muscle

Answer 3

1. add strength

2. permit direct transmission of electrical signals from cell to cell.

Question 4

Inercalated discs in cardiac muscle

Answer 4

At the ends of the muscle cells. Consist of desmosomes and gap junctions.
Desmosomes hold the cells tightly together.
Gap-junctions form low resistance pathways between cardiac muscle cells.

Question 5

Function of intercalated discs

Answer 5

Heart can function as syncytium, enabling contractile activity to be coordinated to ensure the efficient pumping of blood

Question 6

Sacroplasmic reticulum in cardiac muscle

Answer 6

Less dense SR and less extensive (but larger diameter) T-tubule system than in skeletal muscle.

Question 7

Pacemaker and AP propagation

Answer 7

Localized in the sinoatrial node (SA) in the right atrium
Can depolarize and generate action potentials spontaneously
Propagation via gap junctions and conducting fibers throughout the atria.
Enters to ventricular myocardium through the atrioventricular (AV) node passing throughout ventricular muscle via bundle of His, Purkinje fibers and gap junctions.

Question 8

Length-tension relationship of cardiac muscle

Answer 8

More difficult to stretch cardiac muscle beyond optimal sacromere length.

Question 9

Cardiac action potential (vbentricular myocytes)

Answer 9

At rest K-channels are open and there is an outward K- current (IK). Membrane potential is ~-90mV.
Opening of transient Na-channels induces an inward Na- current (iNa), membrane depolarizes.
Transient K- channels open causing an outward K-current (iKto) and a small repolarization.
Opening of Ca-channels induces and inward Ca- current (iCa(L)).
Membrane remains depolarized until Ca-channels inactivate and K-channels open.

Question 10

Excitation-contraction coupling in cardiac muscle cells

Answer 10

Ca2+ enters the cells via Ca2+ channels in the cell membrane during action potential plateau. This Ca2+ entry (trigger Ca2+) induces more Ca2+ to be released from the sarcoplasmic reticulum (Ca2+ induced Ca2+ release) via Ryanodine receptors (Ca2+ spark).
Ca2+ binding to troponin moves tropomyosin and actin binds to myosin leading to cross-bridge cycling and muscle contraction.
At the end of the action potential plateau, Ca2+ influx is cut off, and Ca2+ is pumped back into the sarcoplasmic reticulum with the help of a Ca2+- pump.
Ca2+ is also removed from the cell by a Na+-Ca2+ exchanger. Na+ is then transported out of the cell by the Na+-K+ pump. The contraction ceases until a new action potential.

Question 11

Nervous input to cardiac myocytes

Answer 11

No motor units: every cell contracts with every beat.
Sympathetic stimulation increases the levels of epinephrine and norepinephrine.
These activate ß-adrenergic receptors in the cardiac muscle cells leading to increased levels of cAMP.
cAMP induces phosphorylation reactions leading to increased activity of voltage activated Ca2+ channels and the SERCA pump resulting into [Ca2+] increase in the sarcoplasmic reticulum.
During the next action potential, more Ca2+ is released leading to 1) greater force of contraction and 2) shorter contraction, increasing the heart rate.

Question 12

Function of smooth muscle

Answer 12

Produces motility in hollow organs: propels material in GI system and urethrer
Maintains tension, restricts flow in blood vessels

Question 13

Smooth muscle structure

Answer 13

Many types
Involuntary
Single nucleus
No striations
No sacromeres
About 10um diameter, 100um long.

Question 14

SR and T-tubules in smooth muscle

Answer 14

SR is minimal, no T-tubules.

Question 15

Are all smooth muscles under nervous control?

Answer 15

No, and the ones that are are very different from those in skeletal muscle

Question 16

Single unit smooth muscle

Answer 16

Muscle fibers are gathered into dense sheets.
Neighboring cells have gap junctions that allow spread of signals throughout the tissue.
Important in organs such as the intestine where extensive areas work together to mix or propel the luminal contents.
Often the whole organ can contract in response to one action potential.
In the uterus, gastrointestinal tract, urether, and bladder.

Question 17

Multiunit smooth muscle

Answer 17

Muscle fibers behave as separate motor units.
Little or no electrical coupling between cells.
One autonomic nerve innervates one unit and this unit functions more or less independently from other units.
In the iris, ciliary muscle of the lens, and vas deferens.
Example: smooth muscle cells associated with hair follicles make your
“hair stand on end” when your sympathetic system is activated.

Question 18

Structure of smooth muscle

Answer 18

Thick filaments composed of myosin
Thin filaments contain actin and tropomyosin, but no actin
Intermediate filaments, gap junction
Myosin heads along entire length - not as bare as skeletal muscle

Question 19

Contracted smooth muscle structure

Answer 19

Dense body

Question 20

Smooth muscle action potentials and generation of force

Answer 20

Action potential generation leads to muscle contraction.

Rhythmic slow wave activity.

Graded changes in Em lead to tonic contractions.

Pharmacomechanical coupling, drugs or hormones induce muscle contraction or relaxation. 1

Question 21

Smooth muscle control system

Answer 21

No motor end-plate regions. Nerve fibers run through the tissue and varicosities along the nerve contain vesicles with transmitter molecules. As the action potential sweeps down the nerve, transmitter is released
at each varicosity.

Question 22

Smooth muscles can be stimulated by these 5 things

Answer 22

1) Spontaneous electrical activity in the muscle fiber plasma membrane.
2) Neurotransmitters released by autonomic nerves. 3) Hormones.
4) Local chemical changes in the environment.
5) Stretch of the muscle fiber.

Muscle activation is initiated by increase in intracellular Ca2+.

Question 23

Excitation-contraction coupling in smooth muscle

Answer 23

[Ca2+] rises and Ca2+ binds to calmodulin.
Active Ca2+-calmodulin complex binds and activates myosin light chain kinase (MLCK).
One of the light chains of each myosin head is phosphorylated by MLCK. When this chain is phosphorylated, the head can bind repetitively with the actin filament and proceed through the cycling process of intermittent “pulls,” and cause muscle contraction.

Question 24

Relaxation of smooth muscle

Answer 24

ATP driven Ca2+ pump removes Ca2+ to the sarcoplasmic reticulum or out of the smooth muscle.
[Ca2+] decreases, Ca2+ is released from calmodulin, myosin is dephosphorylated by phosphatase, myosin detaches from actin and the muscle relaxes.
Significantly slower process than skeletal muscle relaxation

Question 25

Phasic contraction

Answer 25

A brief stimulus leads to elevation of cytosolic [Ca2+]. This is followed by a rapid cross- bridge formation and a fast muscle contraction.

Question 26

Tonic contraction

Answer 26

During prolonged stimulation Ca2+ and phosphorylation levels fall. Contraction is maintained with lower cross- bridge cycling rates (= latch state) manifested by lower shortening velocities and ATP consumption.

Question 27

Intracellular calcium in smooth muscle

Answer 27

Hormone or transmitter activates Phospholipase C (PLC) to produce IP3 (from PIP2), which induces Ca2+ release from sarcoplasmic reticulum.
• Hormones and transmitters may also activate ligand- gated Ca2+ channels on the sarcolemma.
• Action potential on the cell membrane may induce Ca2+ influx via voltage-gated Ca2+ channels.
• Ca2+ re-accumulates to SR by SERCA pump or is extruded from the cell.

Question 28

Length-tension relationship compared across muscle types

Answer 28

A. In skeletal muscle, stimulus leads always to a full twitch contraction. B. Smooth muscle contraction varies depending on the resting length (length adaptation).
C. Probably due to change in the contractile units