S1B5 - Smooth Muscle

Question 1

Decreased intracellular calcium concentrations and stimulation of myosin light chain phosphatase leads to what process in smooth muscle cells?

Answer 1

Smooth muscle relaxation occurs with the removal of the contractile stimulus. This quickly results in decreased intracellular calcium concentrations and stimulation of the enzyme myosin light chain phosphatase.

Question 2

How can smooth muscle cells be differentiated from cardiac and skeletal muscle on histological sections?

Answer 2

Histologically, smooth muscle cells can be distinguished from cardiac and skeletal muscle because they lack a striated banding pattern.

Question 3

Which other type of muscle cell (cardiac or skeletal) is under similar neuronal control as smooth muscle cells?

Answer 3

Smooth muscle is similar to cardiac muscle which is also under involuntary, autonomic control. However, it differs from skeletal muscle which is under voluntary, somatic control.

Question 4

What is the name of the enzyme that removes the high-energy phosphate from the light chain of myosin to promote smooth muscle relaxation?

Answer 4

In addition to the Ca2+-dependent activation of myosin light chain kinase, the state of myosin light chain phosphorylation is further regulated by myosin light chain phosphatase. This enzyme removes the high-energy phosphate from the light chain of myosin to promote smooth muscle relaxation.

Question 5

Phosphorylation of the myosin light chain has what effect on smooth muscle contraction?

Answer 5

Phosphorylation of the light chain of myosin allows contraction of smooth muscle to occur.

Question 6

For smooth muscle contraction to occur, which enzyme must become activated?

Answer 6

Membrane depolarization of the smooth muscle cell activates the enzyme myosin light chain kinase (MLCK) which acts to phosphorylate the light chain of myosin. This enables the molecular interaction between myosin with actin.

Question 7

Is contraction of smooth muscle initiated by change in the thick or thin filaments?

Answer 7

Contraction of smooth muscle is initiated by a Ca2+-mediated change in the thick filaments. Recall, thick filaments are myosin motor proteins, thin filaments are made of actin.

Question 8

Name the four primary locations that smooth muscle is found in the body.

Answer 8

Smooth muscle cells are primarily contained in the:

• Cardiovascular system (tunica media of blood vessels)
• Gastrointestinal system (stomach, intestines, ducts, sphincters)
• Genitourinary tract (bladder, sphincters, uterus)
• Upper and lower respiratory tracts

Question 9

Is smooth muscle contraction under voluntary or involuntary control?

Answer 9

The process of smooth muscle contraction is under involuntary control.

Question 10

In the process of smooth muscle contraction, intracellular calcium ions form a complex with which protein?

Answer 10

With increased intracellular concentrations in the smooth muscle cell, the Ca2+ ions can combine and form a complex with the acidic protein calmodulin.

Question 11

Name the two primary mechanisms that can trigger depolarization of the membrane potential in smooth muscle cells.

Answer 11

Regulation of the contractile process is primarily controlled through two mechanisms:

• Receptor-mediated depolarization of the plasma membrane
• Activation of stretch-dependent ion channels in the plasma membrane.

Question 12

Which ion is the primary initiator of the contractile process in smooth muscle cells?

Answer 12

In smooth muscle contraction, the release of calcium ions (Ca2+) is the primary signal for triggering the contraction and cross-bridge cycling between actin and myosin. Release of calcium ions can be stimulated by hormones, neurotransmitters, or signaling between myocytes. (Remember: “Ca2+ -> Contraction”)

Question 13

What effect do increased levels of cGMP have in smooth muscle cells?

Answer 13

Smooth muscle relaxation can also occur through nitric oxide-mediated stimulation of guanylate cyclase activity, which leads to increased cGMP-induced smooth muscle relaxation. Increased levels of cGMP promote myosin light chain phosphatase activity. (Remember: “Nitric oXide -> RelaXation”).

Question 14

In smooth muscle contraction, what enzyme activates myosin light chain kinase?

Answer 14

The Ca2+-calmodulin complex activates myosin light chain kinase (MLCK), which allows it to phosphorylate the light chain of myosin. Recall, phosphorylated myosin motor protein leads to smooth muscle contraction via sliding of actin filaments.

Question 15

What do smooth muscle cells use Ca,Mg-ATPases for during the process of relaxation?

Answer 15

In order to decrease intracellular Ca2+ concentrations, smooth muscle cells use Ca,Mg-ATPases to sequester intracellular Ca2+ into the sarcoplasmic reticulum, or to pump calcium ions into the extracellular space.

Question 16

Which of the following molecules actively inhibits smooth muscle contraction?

A) Calmodulin

B) Troponin C

C) Myosin light-chain kinase

D) Myosin light-chain phosphatase

E) Tropomyosin

Answer 16

Myosin light-chain phosphatase

Answer Explanation

Smooth muscle contraction occurs when MLCK (myosin light-chain kinase) phosphorylates myosin light chains, thereby potentiating crossbridge cycling between myosin and actin. The action of MLCK is countered by myosin light-chain phosphatase, which dephosphorylates the myosin light chains thereby inhibiting the contraction.

Calmodulin plays a role in smooth muscle contraction but not its inhibition: stimulation of muscle increases intracellular calcium, which complexes with calmodulin and leads to the calmodulin-calcium complex activates MLCK.

Question 17

What effect do nitrates and phosphodiesterase inhibitors have on cGMP levels in smooth muscle cells?

Answer 17

Pharmacologically, we can increase cGMP-mediated smooth muscle relaxation through administration of Nitric Oxide (nitrates) or Phosphodiesterase Inhibitors (PDE5).

Question 18

Which system provides the innervation of smooth muscle cells?

Answer 18

Smooth muscle contraction receives neural innervation from the autonomic nervous system.

Question 19

Name two mechanisms through which intracellular calcium concentrations can be increased in order to initiate contraction in smooth muscle cells.

Answer 19

In smooth muscle cells, cytosolic Ca2+ is increased through release from intracellular stores (sarcoplasmic reticulum) as well as entry from the extracellular space through Ca2+ channels (receptor-operated Ca2+ channels).

Question 20

What are two intemediate filament components of the smooth muscle cytoskeleton?

Answer 20

Intermediate filaments are cytoskeletal elements which form a structural backbone against which contraction occurs. Desmin and vimentin are 2 protein components of this cytoskeleton.

Question 21

What are the smooth muscle functional analogues to z-lines in striated muscle?

Answer 21

Dense bodies contain the protein actinin and are functionally analogous to zlines in striated muscle. They serve as anchors for the thin-filament protein actin.

Question 22

What types of junctions are found between smooth muscle cells?

Answer 22

Gap Junctions allow direct electrical communications between adjacent smooth muscle cells. Their density varies from tissue to tissue. Mechanical junctions also attach adjacent smooth muscle cells.

Question 23

Which type of muscle cells do not have T-tubules or a terminal cistern system?

Answer 23

Smooth muscle contains no T-tubules and no terminal cistern system. This feature correlates with its small size and its unique lack of dependence on a muscle action potential for inducing contraction.

Question 24

What are smooth muscle cells more dependent on: SR calcium ions or extracellular calcium ions?

Answer 24

Sarcoplasmic reticulum is relatively poorly developed. Therefore, smooth muscle is more dependent on an extracellular Ca++ source for contraction than cardiac (partial-dependence) or skeletal muscle (negligible-dependence).

Question 25

Tropomyosin and troponin: * Which is associated with smooth muscle actin and which isn't?

Answer 25

**Tropomyosin is** associated with smooth muscle actin. **No troponin is** associated with smooth muscle actin (remember troponin-I inhibits cross-bridge cycling in striated muscle).

Question 26

Is smooth muscle regulation coupled to Ca++ levels through an actin-based mechanism or a myosin based mechanism?

Answer 26

Although caldesmon and calponin are actin binding proteins whose phosphorylation can modulate smooth muscle contraction by affecting ATPase activity, classic thinking is that smooth muscle regulation differs from striated muscle regulation in that it is coupled to Ca++levels through **myosin-based mechanism.**

Question 27

Smooth muscle myosin: * How many heavy chains? * How many light chains? * Which ones are regulatory?

Answer 27

Myosin has six subunits: **two paired heavy** chains each composed of a head and a tail region; and **4 light-chains** associated with the head region of the heavy chain. Light chains serve an ***_essential_*** **regulatory function in smooth muscle** but probably not striated muscle.

Question 28

What's different between the myosin arrangement in smooth muscle and that of striated muscle?

Answer 28

Smooth muscle myosin is thought to be organized in a **side-polar arrangement** as opposed to the bipolar arrangement seen for striated muscles. This likely contributes to smooth muscles’s lack of well-defined sarcomeres.

Question 29

What are the two types of smooth muscle?

Answer 29

**Single unit** smooth muscle organs. Also called unitary or visceral smooth muscle. This type of smooth muscle behaves in a **syncytial manner** much like cardiac muscle. **Multiunit** smooth muscle organs. Each smooth muscle cell acts **relatively independently** of other smooth muscle cells in the organ. In this sense multiunit smooth muscle is like skeletal muscle.

Question 30

Organs with this type of muscle include: small intestine, colon, uterus (myometrium), urinary bladder, ureters, lymph vessels, and smaller arterioles.

Answer 30

**Single unit** smooth muscle organs

Question 31

What smooth muscle type tends to have many gap junctions between cells with sparse innervation?

Answer 31

**Single unit** smooth muscle organs

Question 32

Slow wave potentials are associated with what type of smooth muscle organs?

Answer 32

**Single unit** smooth muscle organs * **Slow Wave Potentials.** There is spontaneous, graded oscillation in membrane potential that is rhythmical in nature. These graded depolarizations sometimes cause contraction and sometimes do not. Graded potentials can also lead to action potential (all or none) spikes. When action potentials occur there is almost always an associated contraction.

Question 33

Plasticity is associated with what type of smooth muscle organs?

Answer 33

**Single unit** smooth muscle organs * **Plasticity.** Slow stretch of single unit organs leads to lengthening of smooth muscle. This is what allows the **bladder** to hold urine (up to a point) without a substantial increase in pressure. This is also called “**stress relaxation**”.

Question 34

Stretch induced contraction is associated with what type of smooth muscle organs?

Answer 34

**Single unit** muscle organs * **Stretch induced contraction**. Fast stretch causes depolarization and leads to contraction

Question 35

Organs with what type of smooth muscle include: ciliary muscle, iris muscles, bronchial muscle, tracheal muscle, vas deferens, GI sphincters, and larger blood vessels?

Answer 35

**Multiunit** smooth muscle organs

Question 36

Which type of smooth muscle tends to have less gap junctions and higher innervation ratios?

Answer 36

**Multiunit** of smooth muscle tends to have **less gap junctions** between cells making each cell operated independently. Multiunit smooth muscle tends to have **higher innervation ratios** than in visceral smooth muscle.

Question 37

Which type of smooth muscle does not typically sisplay action potentials when stimulated to contract?

Answer 37

The membrane potential of **multiunit** smooth muscle is stable with no spontaneous depolarization. Typically, such tissues do not display action potentials when stimulated to contract.

Question 38

What effect does progesterone have on myometrial smooth muscle cells?

Answer 38

Hormones can change the basic character of smooth muscle. For example, high **progesterone** levels during pregnancy **reduce the number of gap junctions** in myometrial smooth muscle, make it behave more like **noninnervated multiunit** smooth muscle, and render it **relatively quiescent**.

Question 39

What effect does rising estrogen leves during term pregnancy have on myometrial smooth muscle cells?

Answer 39

At term, rising **estrogen** levels cause **smooth muscle hypertrophy** and **increase the number of gap junctions.** This allows the muscle to behave more as a **single unit smooth muscle** and participate in parturition.

Question 40

What is latch state in smooth muscle and what is it similar to in striated muscle?

Answer 40

Model of the **Latch State**. * This is a special state that allows smooth muscle to **maintain tone (force)** with **minimal expenditure of ATP.** Shortening is not occurring. * If myosin light chains are dephosphorylated myosin ATPase activity decreases. This means that it is more difficult to release myosin heads from actin which requires ATP hydrolysis. * The myosin heads that stay attached can hold force at the muscle ends. (Think of this latch state as analogous to **rigor** in striated muscle.)

Question 41

Does smooth muscle have high or low * efficiency? * economy?

Answer 41

**Efficiency is low** in smooth muscle because energy is required for both control (light chain phosphorylation) and cross bridge cycling during shortening. **Economy is high** because the ATP use is low to maintain force in the absence of external work (shortening). This is the “latch state”.

Question 42

What are the two main types of voltage gated channels found in smooth muscle cells?

Answer 42

**Voltage-gated** plasma membrane channels in smooth muscle. Stimulus for channel opening and closing a change in membrane potential. When channels are open, Ca++ runs into cells since extracellular concentration (10-3 M) is higher than resting intracellular concentration (10-7 M). This triggers contraction. * **L-type (slow)** Ca++ channels * **T-type (fast)** Ca++ channels

Question 43

What are the differences between L-type and T-type Ca++ channels in smooth muscle cells?

Answer 43

**L-type (slow)** Ca++ channels. “L” is for **long acting**. Channels **open slowly and close slowly**. Open at relatively positive membrane potentials. These are the channels **affected by “Ca++-channel blockers”** (e.g. verapamil, nifedipine, and diltiazem). **T-type** (fast) Ca++ channels. “T” is for **transient**. These channels **open and close quickly**. Rapid influx from these channels may be key to Ca++-induced Ca++ release from the sarcoplasmic reticulum which is **dependent on rate of change** of Ca++ concentration not absolute Ca++ concentration. **Not blocked** by usual Ca++ channel blockers.

Question 44

How do ATP-sensitive K+ channels behave in the presence of normal intracellular ATP?

Answer 44

ATP-sensitive K+-channels. This is a class of K-channels that **remain closed** in the presence of normal intracellular [ATP]i.

Question 45

What is the effect of ischemia on ATP-sensitive K+ channels?

Answer 45

Ischemia can **decrease the intracellular [ATP]i,** **open these K+-channels**, and **hyperpolarize** the membrane.

Question 46

What is the overall effect of hyperpolarization on smooth muscle?

Answer 46

Hyperpolarization closes voltage gated, L-type Ca++ channels, reduces Ca++ influx, and **relaxes the smooth muscle.**

Question 47

ACh acting of m2 receptors and adenosine actine on A1 receptors will activate what kind of smooth muscle ion channels\>

Answer 47

Agonists which activate **G-protein-coupled K+** channels include ACh acting on m2 receptors and adenosine acting on A1 receptors.

Question 48

What is the net effect on smooth muscle when the Gαi subunit that is released directly binds to G-protein-coupled K+ channels?

Answer 48

The Gαi subunit that is released directly binds these K-channels and **opens** them. The cell hyperpolarizes. L-type Ca++ channels are inactivated (closed). **Relaxation occurs.**