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Electrical excitability of cells > Smooth muscle innervation > Flashcards

Smooth muscle innervation Flashcards

1
Q

What is the rough Em of smooth muscle cells?

A

-50mV

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2
Q

Compare APs in smooth and skeletal muscle

A

Smooth - Slower upstroke and last longer

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3
Q

What current drives depol in SMC?

A

L Ca2+ current

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4
Q

What repolarises smooth muscle cells?

A

Ca2+ activated K+ channel and VGKC

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5
Q

Why is SM nerve transmission described as “en passant”

A

APs pass along neurone across each varicosity releasing neurotransmitter into synaptic cleft

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6
Q

How is visceral SM similar to SAN?

A

Can exhibit pacemaker activity

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7
Q

Describe what triggers contraction in single unit SM?

A

Pacemaker cells - spontaneous contraction.

Modified by ANS and neurotransmitters etc

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8
Q

Describe what triggers activation of multiunit SM?

A

Motor neurones (contraction initiated by neurotransmitter)

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9
Q

True of false, VGNC drives SM action potential?

A

False, it’s Ca2+ (L type)

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10
Q

How do SM open SR (what mechanism)?

A

Intracellular signals, i.e. secondary messenger system

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11
Q

What are 3 mechanism for Ca2+ increase in SM?

A

Ligand gated ion channel

Ca2+ via L type channel (NA = agonist and depolarise cell membrane)

IP3 mediated Ca2+ release from SR

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12
Q

Instead of troponin, what initiates contraction in SM?

A

Myosin phosphorylated which activates its ATPase ability

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13
Q

Does SM need changes in Em for contraction?

A

No

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14
Q

What does tropomyosin do at rest?

A

Blocks myosin binding site, stabilises actin

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15
Q

What is functionally similar to troponin?

A

Caldesmon - regulates position of tropomyosin

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16
Q

Describe structure of myosin

A

2 heavy chains, 4 light chains head, hinge and tail region

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17
Q

Which part of myosin forms cross bridge with actin?

A

Head

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18
Q

What part of myosin has ATPase activity?

A

Head

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19
Q

In absence of Ca2+ what prevent actin myosin binding?

A

Myosin light chain (not tropomyosin)

20
Q

True or false, tropomyosin stops actin myosin binding when Ca2+ absent (SM)?

A

False, it’s Myosin light chain

21
Q

How many Ca2+ bind to calmodulin?

A

4

22
Q

What does Ca2+ bind to?

A

Calmodulin

23
Q

What 3 things does CalCam act on, what are the effects?

A

Activates MLCK - MLCK phosphorlylates P light chain of myosin (MLC)

CalCam acts on caldesmon removes inhibition of tropomyosin

Calcam binds to calponin -removes inhibiton on myosin head ATPase activity

24
Q

Which part of myosin regulates cross bridge cycling?

A

P light chain

25
Q

What happens after MLC phosphorylated?

A

Relieves MLC inhibition and ATP hydrolysed by myosin head and cross bridge cycling occurs

26
Q

What happens in relaxation?

A

Dephos of MLC by MLCP when Ca2+ falls

27
Q

What are the roles of PKA and PKG in smooth muscle relaxation on MLCK?

A

Phophorylate MLCK (inactive)

Reduce Ca2+ sensitivity of MLCK - more calcium calmodulin needed to activate it

Promote relaxation

28
Q

How do PKA and PKG promote relaxation?

A

Phosphorylate/desensitise MLCK

Phosphorylate K+ channel to hyperpolarise membrane inhibits Ca2+ entry

29
Q

What are the roles of calponin and caldesmon (how do they compare to troponin/tropomyosin)?

A

Caldesmon (tropomyosin) and calponin (inhibits heads ATPase activity)

30
Q

What does DAG subunit do to release Ca2+/promote contraction?

A

DAG, along with Ca2+, activates protein kinase C (PKC) which promotes contraction/Ca2+ entry

31
Q

What does PKC do?

A

Phosphorylates L-type Ca2+ channels

Phosphorylates MLCP (inhibits it)

32
Q

What inhibits MLCP?

A

PKC

33
Q

What is the effect of decreasing Ca2+ in SM contraction?

A

Inactivates MLCK

34
Q

What does Rhokinase do?

A

Inhibit MLCP (increased sensitization)

35
Q

What is meant by SM being in latch state?

A

Uncoupling of actin and myosin slow - latch process. (after MLC dephos)

36
Q

What is the benefit of latch mechanism?

A

Tension generated for longer period (sustained contraction) at low energy cost and at low Ca2+

37
Q

How does para and symp promote contraction (neurotransmitter and receptor)?

A

Para: Ach: M3
Symp: NA: alpha 1

38
Q

How can symp system inhibit SM contraction?

A

NA on beta 2

39
Q

Which cells secrete NO?

A

Endothelial cells

40
Q

What GPCR is stimulated, and by what in the NO synthesis pathway?

A

M3 by ACh

41
Q

Pathway for NO production

A

ACh - M3 - Ca2+ calmodulin, activate eNOS - L arginine to L citrulline - release NO

42
Q

What does NO do after being made in endothelial cells (give pathway)?

A

NO diffuse to tunica media in SMC

Stimualte cGMP, activate PKG,

43
Q

What activates MLCK?

A

Calcium-calmodulin complex

44
Q

What generates acetylcholine-induced contraction of ileal smooth muscle?

A

IP3 increase

45
Q

What generates isoprenaline-induced relaxation of bronchial smooth muscle?

A

cAMP increase

46
Q

How does raised cAMP (bronchiolar smooth muscle) cause relaxation?

A

cAMP relaxes bronchiolar smooth muscle phosphorylating myosin light chain kinase.

47
Q

Does smooth muscle have gap junctions?

A

Yes

Electrical excitability of cells (9 decks)

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