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Cardiovascular and Respiratory > 3) respiration - control of airway smooth muscle > Flashcards

3) respiration - control of airway smooth muscle Flashcards

1
Q

what are the 4 steps in contraction of smooth muscle

A
  1. Increase in cytoplasmic calcium levels
  2. Calcium binds to calmodulin (CM) forming a calcium-calmodulin complex
  3. Calcium-calmodulin activates myosin light chain kinase
  4. MLCK now in a phosphorylated state allows muscle contraction
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2
Q

what does. calcium bind to in smooth muscle

A

calmodulin

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3
Q

purpose of calcium-calmodulin in Smooth muscle contraction

A

activates myosin light chain kinase

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4
Q

how does relaxation occur

A

myosin light chain phosphatase dephosphorylates MLCK

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5
Q

what is airway smooth muscle functioning dependant on

A

GPCR cascades

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6
Q

function of Qq pathway in smooth muscle

A

contraction

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7
Q

outline the Gq pathway

A
  1. Agonist binds to the receptor
  2. Activated form of Gq alpha subunit, stimulates phospholipase-C
  3. Phospholipase-C acts on PIP2, forms DAG and IP3
  4. IP3 stimulates release of calcium from stores and at the same timeget calcium influx
  5. Calcium binds. to CM, CM activates MLCK which phosphorylates smooth muscle causing contraction
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8
Q

what are the. 3 receptors involved in the Gq pathway

A

M3 muscarinic receptors
H1 histamine receptors
BK bradykinin receptors

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9
Q

function of the Gs pathway in smooth muscle

A

relaxation

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10
Q

outline the Gs pathway

A
  1. Binding of agonist to receptor, activates Gs alpha subunit
  2. Activates adenylate cyclase, increases cAMP, stimulates PKA
  3. Inhibits. MLCK, stimulates phosphates and relaxes muscle
  4. also activates potassium channels, potassium leaves the cell causing hyperpolarisation, membrane more negative, reduces calcium influx
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11
Q

receptors. involved in Gs. pathway

A

B2 adrenergic receptors

vasointestinal peptide receptors

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12
Q

function of the Gi pathway in smooth muscle

A

counteracts Gs pathway

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13
Q

outline the Gi pathway

A
  1. activation of Gi receptors leads to inhibition of Adenylate cyclase
  2. knock on effect is to counteract the stimulatory effect of Gs activation
  3. opposes relaxation of smooth muscle
  4. also inhibits the BK potassium channel
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14
Q

receptor involved in the Gi pathway

A

M2 muscarinic receptors

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15
Q

outline the parasympathetic control of smooth muscle

A

parasympathetic control leads to Ach release by the postganglionic fibres which causes contraction of airway smooth muscle.
M1 and M3 receptors on epithelial cells. are also stimulated to increase mucous production

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16
Q

outline the smooth muscle contraction via M3 receptors

A

release of Ash, binds to M3 receptors on ASM, activates the Gq pathway leading to smooth muscle contraction

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17
Q

what type of system is airway smooth muscle contraction.

A

negative feedback

Ach binds to M2 receptors on the preganglionic neuron preventing over release of Ach

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18
Q

function of sympathetic nervous system on ASM

A

ASM relaxation

19
Q

receptors targeted by sympathetic nervous system on ASM

A

B2 adrenoreceptors on ASM

20
Q

what in NANC signalling

A

noradrenergic/norcholinergic. signalling

21
Q

what are the 2 pathways of NANC signalling

A

excitatory (eNANC) and inhibitory (iNANC)

22
Q

effect of eNANC

A

bronchoconstriction

23
Q

effect of iNANC

A

brochorelaxation

24
Q

transmitters. involved in eNANC

A

vasointestinal peptide
nitric oxide
neuropeptide Y

25
Q

transmitters involved. in iNANC

A

substanceP/. Neurokinin A

26
Q

define asthma

A

a common chronic disorder. of the airways that is complex and characterised by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness and an underlying inflammation

27
Q

what is atopic asthma

A

extrinsic - associated with allergies

linked to elevated levels of serum IgE and positive skin test

28
Q

in atopic asthma what occurs upon presentation of allergen

A

activation of mast cells
release of inflammatory mediators including histamine
can lead to activation of other inflammatory cells such as eosinophils

29
Q

what is non-atopic asthma

A

intrinsic - no positive skin test and normal serum IgE levels

induced by a variety of factors - exercise, cold air, inhaled irritants, stream drugs
linked to localised increase in IgE production

30
Q

is asthma associated with an increase in parasympathetic or. sympathetic activity

A

parasympathetic

31
Q

what happens to basal tone and muscle constriction in asthma

A

increase

32
Q

what is released from parasympathetic nerve and epithelial cells in asthma

A

Ach

33
Q

where does Ach bind in asthma

A

M3 in ASM
M1 and M3 in submucosal glands
white blood cells

34
Q

effect of Ach to ASM

A

bronchoconstriction, airway hyperactivity, ASM thickening, ECM deposition

35
Q

effect of Ach to submucosal glands

A

increase mucous production and remodelling of goblet cells

36
Q

effect of Ach to white. blood cells

A

triggers inflammation

37
Q

how does an increase in parasympathetic activity affect M1, M3 and M3 receptors

A

no change in M1 or M3

decrease in neuronal M2 function

38
Q

what happens to eosinophils in asthma

A

eosinophils cluster around the nerve fibres

39
Q

what do activated eosinophils release

A

major basic protein (MBP)

40
Q

what does MBP do

A

MBP inhibits M2 receptors (prevents negative feedback mechanism), therefore too much Ach is released, activates M3 causing further ASM constriction and increases long term mucous secretion

41
Q

what is asthma treated. with

A

anticholinergics

42
Q

actions of anticholinergics

A

blocks effects of endogenous Ach
short and long lasting]competitive inhibitors of M1,2,3 receptors
dissociate more slowly from M3

43
Q

outline short term asthma treatment

A

ipratropium - used in combination with short acting B2-adrenoceptor agonists

44
Q

outline long lasting asthma treatment

A

Tiotropium. - used in combination with long acting B2-adrenoceptor agonists and inhaled corticosteroids - inhaled once. daily with actions against M1 and 3 receptors

Cardiovascular and Respiratory (4 decks)

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