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Physiology > Smooth Muscle (B 2: W 2) > Flashcards

Smooth Muscle (B 2: W 2) Flashcards

1
Q

Describe the size and shape of smooth muscle cells

A

3-6 µm in diameter and 100-500 µm in length

Spindle-shaped

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2
Q

What is the significance of the surface to volume ratio of smooth muscle cells?

A

Large surface to volume reatio is important

Calcium from the outside can change the concentration within the cell quickly

1.5-2.5 µm2 surface to µm3 volume

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3
Q

What are dense bodies and dense bands?

A

Structures associated with the membrane, where contractile and cytoskeleton proteins are anchored to the cell surface

  • Dense bands are often coupled to other cells or to the extracellular matrix
  • Dense bodies are found within the cytoplasm
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4
Q

What are caveolae?

A

Flask-shaped invaginations of smooth muscle plasma membrane

  • Make up about 50% of membrane present at cell surface
  • Thousands per cell - adds about 60% to the amount of plasma membrane to the cell surface
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5
Q

Where can you find the plasmalemmal Ca-ATPase pump that extrudes calcium from the smooth muscle cell and helps maintain homeostasis?

A

Localized within the caveolae

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6
Q

Which structures are the caveolae in this EM figure?

A

The little white dots around the edge of the smooth muscle cells are caveolae

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7
Q

What is the function of gap junctions?

A

A gap junction is a low resistance pore

  • Produce low electrical resistance pathways between cells
    • Connect smooth muscle cells electrically
  • Ions can move from cell-to-cell via gap junctions
  • Allow smooth muscles to act as a syncytium
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8
Q

What is the structure of gap junctions?

A

Formed of hexameric (6) assemblies of proteins called connexins

These proteins form aqueous pores known as hemichannels, or connexons (as many as 10) - half of the channel

Gap junctions contain several hundred connexins

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9
Q

Which is the most important gap junction protein in smooth muscle cells?

A

Connexon 43

Several other isoforms of gap junction proteins are present and may contribute to the overall connectivity between cells

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10
Q

What are the different ways in which smooth muscle is regulated?

A
  • Myogenic mechanisms - spontaneous activation in the absence of stimuli
  • Neural regulation
  • Hormonal regulation
  • Humoral or paracrine - substances produced in immediate environment of cells affect contractility
  • Inflammatory mediators - agents released by inflammatory cells can affect smooth muscle contractility
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11
Q

How is the actin-myosin cross-bridge activated in smooth muscle?

A
  • Calcium binds to calmodulin
    • Activates myosin light chain kinase MLCK
  • MLCK phosphorylates the 20 kDa light chain of myosin (MLC20)
    • Facilitates actin binding and cross-bridge cycling
  • ATP binding to the head causes release
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12
Q

How does smooth muscle relax from the cross-bridge?

A
  • Phosphorylation of MLC20 is balanced by myosin (light chain) phosphatase (MLCP).
    • MLCP dephosphorylates MLC20
    • Reduces cross-bridge cycling
    • Relaxation
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13
Q

Why is smooth muscle cross-bridge cycling much slower than in striated muscle?

A

Myosin ATPase is much slower

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14
Q

What does smooth muscle use instead of tropoinin?

A

Calmodulin

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15
Q

What determines the force and duration of contraction in smooth muscle?

A

The balance between myosin phosphorylation and dephosphorylation

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16
Q

What happens when there is an increase in activation in MLCK?

A

Contraction

There is an increase in calcium

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17
Q

What happens when there is an increase in MLCP in smooth muscle?

A

Relaxation

18
Q

What is the main source of calcium influx in the depolarization of smooth muscle cells?

A

Voltage gated Ca channels

19
Q

Aside from voltage dependent Ca channels, what channels provide additional calcium for responses to agonists in smooth muscle cells?

A

NSCC: Non selective cation channels

Also called ROC: receptor-opperated channels

Activated by receptors directly

20
Q

What exchangers and pumps help to maintain gradients in the smooth muscle cell?

A
  • Na-K ATPase - removes Na, adds K
  • Ca ATPase in plasma membrane - removes Ca that enters cells during excitation
  • Sarcoplasmic reticulum Ca ATPase (SERCA) - retrieves Ca into Ca stores
  • Na-Ca exchanger (NCX) - removes Ca from cells (does not use ATP)
21
Q

How is resting membrane potential set in smooth muscle cells?

A
  • Dominant resting permeability in smooth muscle cells is due to potassium channels
  • Ionic gradients across the plasma membrane lead to outward current when K channels are open
    • Loss of K ions causes net negative membrane ptoentials
    • RMP typically between -40 mV and -80 mV
  • Ionic gradients to sustain RMPs are maintained by ion pumps using ATP for energy
22
Q

What 4 types of potassium channels are expressed in smooth muscle cells?

A
  • Voltage gated K channels - 6 transmembrane segments and one pore domain
  • Ca activated K channels - 6 or 7 transmembrane segments
    • Ex: BK, IK, SK
  • KATP, KIR, GIRK channels - 2 transmembrane segments and one pore domain
  • Two-pore K channels (K2P) - 4 transmembrane segments and 2 pore domains
23
Q

How are voltage-gated L-type Ca channels activated?

A

By membrane potential

Depolarization causes activation of L-type Ca channels

Ca entry happens above -60 mV

24
Q

Do action potentials occur in an isolated smooth muscle cell?

A

Yes

Generation of action potentials occurs at irregular frequencies (top graph)

25
Q

What is dilitazem?

A

Ca channel blocker (L-type)

Action potentials stop with the adition of dilitazem

(Applied at the beginning of bottome trace)

26
Q

Does a single Ca channel regulate behavior of smooth muscle?

A

No

Several Ca dependent ion channels regulate behavior

They can cause conflicting reactions

Ca release from the sarcoplasmic reticulum can cause activation or inhibition, depending on the channels present

27
Q

How are BK channels activated and what happens when they open in smooth muscle cells?

A
  • Localized high Ca concentration opens BK channels on SR membrane
  • There is a spontaneous transient outward current - causes the cell to hyperpolarize
    • Hyperpolarization decreases the opening of voltage-gated L-type Ca channels
  • Localized Ca release events cause hyperpolarization and cause relaxation in vascular smooth muscle cells
28
Q

What is the key activating step in smooth muscle contraction?

A

Phosphorylation of myosin by MLCK

29
Q

A rise in intracellular Ca activates the contractile apparatus in smooth muscle cells. What are different mechanisms for this?

A

There are a mixture of mechanisms, depending on the system

  • ROC: receptor operated Ca channels
  • VDCC: voltage dependent Ca channels
  • GPCRs
    • Gq –> Phospholipase C –> IP3 –> SR –> Calcium
30
Q

How are 2nd messengers in smooth muscle cells generated?

A

Receptor coupling - regulates smooth muscle functions

  • G protein coupled receptors
  • NO coupled throug guanylyl cyclase
  • Ion channels in the plasma membrane
31
Q

Which major neurotransmitters control vascular smooth muscles

A
  • Neuronal action potentials promote the release of ATP and norepinephrine from perivascular nerve terminals
    • NE stimulates alpha 1 adrenergic receptors
    • ATP binds to P2X receptors, giving rise to Ca
  • Both cause contraction
32
Q

What is the purpose of the calcium sensitization pathway?

A

Increases the effectiveness of calcium in contractions

Can get a biochemical effect where a small amount of Ca creates a large reaction

Desensitization is the opposite - large amount of Ca creates a small reaction

33
Q

What mechanisms are involved in G protein coupled sensitization?

A

These mechanisms decrease the activity of myosin light chain phosphatase (MLCP), maintaing MLC20 phosphorylation and contraction

Increase the calcium sensitivity of the contractile apparatus

34
Q

Which two proteins are coupled to GPCRs through calcium sensitization?

A

RhoK and CPI-17

Inhibit the activity of MLCP

Causes contraction

35
Q

What mechanisms are involved in G protein coupled calcium desensitzation?

A
  • Activation of adenylyl (adenylate cyclase)
    • Production of cAMP
    • Activation of protein kinase A
  • Increases the activity of MLCP
    • Dephosphorylates MLC20
    • Leads to relaxation
36
Q

Which protein is coupled to GPCRs through desensitization?

A

Telokin

  • Stimulates phosphatase
  • Depopshorylates myosin
  • Causes relaxation
37
Q

How do inhibitory agonists alter the relationship between calcium concentration and force?

A

Reduce calcium sensitivity

Rightward shift in graph (red)

Higher amount of calcium required

38
Q

How do excitatory agonists alter the relationship between calcium concentration and force?

A

Cause calcium sensitization

Leftward shift on graph (green)

Lower calcium concentration causes a contraction

39
Q

How do inhibitory agonists affect excitation-contraction coupling?

A

Protein kinase G and A activate a variety of K channels in smooth muscles

  • Increase in K efflux causes hyperpolarization
  • Decreases opening of voltage gated Ca channels
  • Reduces Ca entry and contraction
40
Q

How does NO cause vasodilation?

A
  • Nitroglycerine causes release of NO
  • Binds to soluble guyanlyl cyclase (sGC) and generates cGMP
  • cGMP activates PKG
  • PKG phosphoylates several cell proteins
  • Proteins phosphorylated by PKG:
    • Inhibit Ca release from IP3 receptors
    • Inhibit activation of L-type Ca channels
    • Increase Ca uptake by SR
    • Activate MLCP (Ca desensitization)
41
Q

How is nitric oxide (NO) synthesized?

A
  • Ca activates endothelial nitric oxide synthase (eNOS)
  • eNOS generates NO from L-arginine
42
Q

What mechanisms restore resting calcium concetration in smooth muscle cells following contraction?

A

Relaxation depends on 3 mechanisms to reduce Ca

  1. SR Ca pump
    1. Protein that exists within SR membrane
    2. Uses ATP to pump Ca from cytoplasm into SR - up steep electrochemical gradient
  2. Plasma membrane Ca pump
    1. Pumps Ca from cytoplasm to outside
    2. Pumps Ca up electrochemical gradient using ATP
  3. Na/Ca exchanger (NCX)
    1. Transports Ca out and Na in
    2. Uses Na gradient

Physiology (29 decks)

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