Smooth muscle innervation

Question 1

What is the rough Em of smooth muscle cells?

Answer 1

-50mV

Question 2

Compare APs in smooth and skeletal muscle

Answer 2

Smooth - Slower upstroke and last longer

Question 3

What current drives depol in SMC?

Answer 3

L Ca2+ current

Question 4

What repolarises smooth muscle cells?

Answer 4

Ca2+ activated K+ channel and VGKC

Question 5

Why is SM nerve transmission described as “en passant”

Answer 5

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

Question 6

How is visceral SM similar to SAN?

Answer 6

Can exhibit pacemaker activity

Question 7

Describe what triggers contraction in single unit SM?

Answer 7

Pacemaker cells - spontaneous contraction.

Modified by ANS and neurotransmitters etc

Question 8

Describe what triggers activation of multiunit SM?

Answer 8

Motor neurones (contraction initiated by neurotransmitter)

Question 9

True of false, VGNC drives SM action potential?

Answer 9

False, it’s Ca2+ (L type)

Question 10

How do SM open SR (what mechanism)?

Answer 10

Intracellular signals, i.e. secondary messenger system

Question 11

What are 3 mechanism for Ca2+ increase in SM?

Answer 11

Ligand gated ion channel

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

IP3 mediated Ca2+ release from SR

Question 12

Instead of troponin, what initiates contraction in SM?

Answer 12

Myosin phosphorylated which activates its ATPase ability

Question 13

Does SM need changes in Em for contraction?

Answer 13

No

Question 14

What does tropomyosin do at rest?

Answer 14

Blocks myosin binding site, stabilises actin

Question 15

What is functionally similar to troponin?

Answer 15

Caldesmon - regulates position of tropomyosin

Question 16

Describe structure of myosin

Answer 16

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

Question 17

Which part of myosin forms cross bridge with actin?

Answer 17

Head

Question 18

What part of myosin has ATPase activity?

Answer 18

Head

Question 19

In absence of Ca2+ what prevent actin myosin binding?

Answer 19

Myosin light chain (not tropomyosin)

Question 20

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

Answer 20

False, it’s Myosin light chain

Question 21

How many Ca2+ bind to calmodulin?

Answer 21

4

Question 22

What does Ca2+ bind to?

Answer 22

Calmodulin

Question 23

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

Answer 23

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

Question 24

Which part of myosin regulates cross bridge cycling?

Answer 24

P light chain

Question 25

What happens after MLC phosphorylated?

Answer 25

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

Question 26

What happens in relaxation?

Answer 26

Dephos of MLC by MLCP when Ca2+ falls

Question 27

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

Answer 27

Phophorylate MLCK (inactive) Reduce Ca2+ sensitivity of MLCK - more calcium calmodulin needed to activate it Promote relaxation

Question 28

How do PKA and PKG promote relaxation?

Answer 28

Phosphorylate/desensitise MLCK Phosphorylate K+ channel to hyperpolarise membrane inhibits Ca2+ entry

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

What does PKC do?

Answer 31

Phosphorylates L-type Ca2+ channels Phosphorylates MLCP (inhibits it)

Question 32

What inhibits MLCP?

Answer 32

PKC

Question 33

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

Answer 33

Inactivates MLCK

Question 34

What does Rhokinase do?

Answer 34

Inhibit MLCP (increased sensitization)

Question 35

What is meant by SM being in latch state?

Answer 35

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

Question 36

What is the benefit of latch mechanism?

Answer 36

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

Question 37

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

Answer 37

Para: Ach: M3 Symp: NA: alpha 1

Question 38

How can symp system inhibit SM contraction?

Answer 38

NA on beta 2

Question 39

Which cells secrete NO?

Answer 39

Endothelial cells

Question 40

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

Answer 40

M3 by ACh

Question 41

Pathway for NO production

Answer 41

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

Question 42

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

Answer 42

NO diffuse to tunica media in SMC Stimualte cGMP, activate PKG,

Question 43

What activates MLCK?

Answer 43

Calcium-calmodulin complex

Question 44

What generates acetylcholine-induced contraction of ileal smooth muscle?

Answer 44

IP3 increase

Question 45

What generates isoprenaline-induced relaxation of bronchial smooth muscle?

Answer 45

cAMP increase

Question 46

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

Answer 46

cAMP relaxes bronchiolar smooth muscle phosphorylating myosin light chain kinase.

Question 47

Does smooth muscle have gap junctions?

Answer 47

Yes