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A Physiology > 1.8. The physiology of smooth muscle. The functions of different types of smooth muscle. > Flashcards

1.8. The physiology of smooth muscle. The functions of different types of smooth muscle. Flashcards

1
Q

I. Physiology of smooth muscle - Smooth muscle
1A. What are the characteristics of smooth muscle?

A
  • Uni-nucleated, narrow, spindle-shaped cells
  • Lacks striations – distinct from cardiac and skeletal muscle, because thin and thick filaments are present, but are not organized in sarcomeres (no Z-lines)
  • No T-tubules, but SR is present
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2
Q

I. Physiology of smooth muscle - Smooth muscle
1B. Where can you find smooth muscle?

A
  • Found in walls of hollow organs: GI-tract, bladder, ureters, bronchioles, vasculature
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3
Q

I. Physiology of smooth muscle - Structure of myofilaments
2A. What are the 2 types of myofilaments?

A

Thin and thick myofilaments

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4
Q

I. Physiology of smooth muscle - Structure of myofilaments
2B. What are the characteristics of thin myofilaments?

A

They contain smooth muscle cell (SMC) actin, tropomyosin (NO TROPONIN)

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5
Q

I. Physiology of smooth muscle - Structure of myofilaments
2C. What are the characteristics of thick myofilaments?

A

Thick – myosin:
- Heavy chain – 2 heavy chains form a complex
- Light chain (MLC) – 2 light chains per heavy chain <- can be phosphorylated by MLCK

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6
Q

I. Physiology of smooth muscle - Types of SMCs
3A. How is the classification of SMCs based on?

A

Classification based on how the cells are electrically coupled

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7
Q

I. Physiology of smooth muscle - Types of SMCs
3B. What are the 2 types of SMCs?

A

1) Single-unit SMCs: (GI-tract & urogenital system)
2) Multi-unit SMCs: (iris, airways, tunica media of large vessels)

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8
Q

I. Physiology of smooth muscle - Types of SMCs
3C1. What are the characteristics of single-unit SMCs

A
  • Has gap junctions which allow easy electrical conduction between cells
  • Gap junctions allow large regions to contract in unison
  • Characterized by spontaneous pacemaker activity – ‘’slow waves’’
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9
Q

I. Physiology of smooth muscle - Types of SMCs
3C2. Where can you find single-unit SMCs?

A

GI-tract & urogenital system

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10
Q

I. Physiology of smooth muscle - Types of SMCs
3D1. What are the characteristics of multi-unit SMCs?

A
  • Each cell has its own innervation
  • Neural control of contraction
  • Functions are tightly regulated
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11
Q

I. Physiology of smooth muscle - Types of SMCs
3D2. Where can you find multi-unit SMCs?

A

Iris, airways, tunica media of large vessels

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12
Q

II. AP in smooth muscle
1. What are characteristics of AP in smooth muscle?

A

Exhibit continuous fluctuation of Em = slow-wave potential
- Occurs as electrical AP generated by interstitial cells of Cajal is propagated through gap junctions
- There are 2 thresholds in SMC Em
+) Threshold for contraction (without having an AP spike)
+) Electrical threshold (AP is generated)

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13
Q

II. AP in smooth muscle
2. What are the 2 thresholds in SMC Em?

A

There are 2 thresholds in SMC Em
1. Threshold for contraction (without having an AP spike)
2. Electrical threshold (AP is generated)

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14
Q

II. AP in smooth muscle
3. How are different types of contraction made?

A

Depending on the degree of depolarization, different types of contractions are made:
- Depolarization does not peak beyond electrical threshold
-> tonic contraction (basal activity)
- Depolarization does reach above electrical threshold
-> phasic contraction (↑AP frequency = ↑ contraction force)

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15
Q

II. AP in smooth muscle
4. What are the 4-step process of SMC AP development?

A
  1. Cationic-leak channels open -> depolarization -> Na+-influx
  2. Electrical threshold is reached
    -> L-type VGCCs open -> a series of AP spikes
  3. ↑[Ca2+]IC causes Ca2+-activated K+-channels to open -> repolarization occurs slowly
  4. VGCCs close due to repolarization -> ↓[Ca2+]IC -> Ca2+-activated K+-channels close
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16
Q

III. Molecular mechanism regulating SM contraction
1. What does contraction depend on?

A

Contraction is dependent on [Ca2+] and the agent that induces contraction by increasing [Ca2+]IC.

17
Q

III. Molecular mechanism regulating SM contraction
2. What are the 3 possible sources of increasing [Ca2+]ic?

A
  1. VG Ca2+-channels
  2. Ligand-gated Ca2+-channels
  3. IP3-gated Ca2+ channels
18
Q

III. Molecular mechanism regulating SM contraction
3. What is the role of Voltage-gated Ca2+ channels in regulation of SM contraction?

A

In the sarcolemma that open during depolarization, taking in EC Ca2+ (unlike skeletal muscle!)
-> will also lead to Ca2+-induced Ca2+-release from the SR

19
Q

III. Molecular mechanism regulating SM contraction
4. What is the role of Ligand-gated Ca2+-channels in regulation of SM contraction?

A
  • Also in the sarcolemma.
  • They are not regulated by the membrane potential, but by receptor-mediated events from hormones or NTs -> extracellular Ca2+-influx
20
Q

III. Molecular mechanism regulating SM contraction
5. What is the role of IP3-gated Ca2+ channels in regulation of SM contraction?

A
  • in the SR membrane.
  • Gq- protein activation triggers the cleavage of PIP2 -> IP3 +DAG
21
Q

IV. Phosphorylation of smooth muscle myosin
1. What is the key signal in regulation of SM contraction?

A

Smooth muscle lacks troponin, which is a key component of skeletal muscle contraction.
=> However, calcium is still the key signal, and smooth muscle regulates contraction via a pathway involving calmodulin:

22
Q

IV. Phosphorylation of smooth muscle myosin
2. What is the 3-step process the regulation of SM contraction by calmodulin?

A
  • Ca2+- ions bind to calmodulin
  • Ca2+-calmodulin complex activates myosin light-chain kinase (MLCK), which phosphorylates myosin light chain, increasing its ATPase activity
    -> Leads to activation of cross-bridge cycling (myosin activated)
  • Have [Ca2+]IC – dependent or independent contraction pathways
23
Q

IV. Phosphorylation of smooth muscle myosin
3. After Ca2+-calmodulin complex is formed, what is the 4-step process of [Ca2+]IC – dependent contraction?

A
  1. An agonist binds to a Gq receptor
  2. Gq/11 stimulates PLC (phospholipase C)
    -> cleaves the membrane-bound PIP2
    -> IP3 & DAG
  3. IP3 binds to IP3-gated-Ca2+-channels in the SR =↑ [Ca2+]IC
    -> Ca2+-calmodulin dependent activation of MLCK
  4. Phosphorylation of MLC by MLCK
    - Rho-GTP activates Rho-kinase -> goes on to
    phosphorylate MLC
24
Q

IV. Phosphorylation of smooth muscle myosin
4. After Ca2+-calmodulin complex is formed, what is the 3-step process of [Ca2+]IC – independent contraction?

A
  • MLCK and Rho-kinase have an additive effect (regulating
    Ca2+ sensitivity)
  1. A G12/13 receptor activates guanine nucleotide exchange factors (GEFs)
    -> goes on to activate Rho-GTP
  2. Rho-GTP stimulates Rho-kinase
    -> inhibits myosin phosphatase (MP)
  3. Decreased MP activity results in an increased level of MLC phosphorylation
25
Q

V. What are the 4 characteristics of SM contraction?

A
  • long lasting Ca2+-signal in the cell
  • contraction requires much less ATP compared to skeletal
    muscle
  • slow actin-myosin cycle in the cell
  • Actin-myosin cross bridges
26
Q

VI. What are the 2 mechanisms inducing SM relaxation?

A
  • cAMP (β2-adrenergic stimulation)
    -> PKA -> induces phosphorylates MLCK -> ↓Ca2+-
    sensitivity = no contraction
  • cGMP (NO-dependent activation) has several
    effects
    1) activation of phosphatase
    2) phosphorylation of IP3 receptor
    3) inhibition of calcium entry into the cell
27
Q

VII. What are the components involved in Termination of Ca2+ signal?

A
  1. The plasma membrane Ca2+ ATPase (PMCA)
    - a transport protein in the plasma membrane of cells and functions to remove calcium (Ca2+) from the cell.
  2. The plasma membrane Na+/Ca2+
    - A single calcium ion is exported for the import of three sodium ions.
  3. SR Ca2+-ATPase (SERCA pump)
    - pump acts to transport calcium ions from the cytosol back to the sarcoplasmic reticulum (SR) following muscle contraction.
28
Q

VIII. What are characteristics of Sliding filament mechanism in smooth muscle?

A
  • Similar to striated muscle
  • Slower contraction
  • Latch-state
29
Q

IX. Phasic versus tonic contraction of SM

A
  • In phasic contraction, [Ca2+]IC , cross-bridge phosphorylation and force reach a peak and return to the baseline
  • In tonic contraction, [Ca2+]IC , cross-bridge phosphorylation decline after a peak but do not return to the baseline -> Latch-state with low energy expedinture
30
Q

X. Modulation of Smooth Muscle
1. List the 6 agonists

31
Q

X. Modulation of Smooth Muscle
2A. Agonist: NE/E (Sym)
Response: ???
Receptor: ???
second messenger: ????

32
Q

X. Modulation of Smooth Muscle
2B. Agonist: Acetylcholine (Parasympathetic)
Response: ???
Receptor: ???
second messenger: ????

33
Q

X. Modulation of Smooth Muscle
2C. Agonist: Angiotensin II
Response: ???
Receptor: ???
second messenger: ????

34
Q

X. Modulation of Smooth Muscle
2D. Agonist: Vasopressin
Response: ???
Receptor: ???
second messenger: ????

35
Q

X. Modulation of Smooth Muscle
2E. Agonist: Endothelin
Response: ???
Receptor: ???
second messenger: ????

36
Q

X. Modulation of Smooth Muscle
2F. Agonist: Adenosine
Response: ???
Receptor: ???
second messenger: ????

A Physiology (88 decks)

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