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

3) respiration - control of airway smooth muscle Flashcards

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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

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A

ASM relaxation

19
Q

receptors targeted by sympathetic nervous system on ASM

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A

B2 adrenoreceptors on ASM

20
Q

what in NANC signalling

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A

noradrenergic/norcholinergic. signalling

21
Q

what are the 2 pathways of NANC signalling

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A

excitatory (eNANC) and inhibitory (iNANC)

22
Q

effect of eNANC

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A

bronchoconstriction

23
Q

effect of iNANC

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A

brochorelaxation

24
Q

transmitters. involved in eNANC

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A

vasointestinal peptide
nitric oxide
neuropeptide Y

25
transmitters involved. in iNANC
substanceP/. Neurokinin A
26
define asthma
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
what is atopic asthma
extrinsic - associated with allergies | linked to elevated levels of serum IgE and positive skin test
28
in atopic asthma what occurs upon presentation of allergen
activation of mast cells release of inflammatory mediators including histamine can lead to activation of other inflammatory cells such as eosinophils
29
what is non-atopic asthma
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
is asthma associated with an increase in parasympathetic or. sympathetic activity
parasympathetic
31
what happens to basal tone and muscle constriction in asthma
increase
32
what is released from parasympathetic nerve and epithelial cells in asthma
Ach
33
where does Ach bind in asthma
M3 in ASM M1 and M3 in submucosal glands white blood cells
34
effect of Ach to ASM
bronchoconstriction, airway hyperactivity, ASM thickening, ECM deposition
35
effect of Ach to submucosal glands
increase mucous production and remodelling of goblet cells
36
effect of Ach to white. blood cells
triggers inflammation
37
how does an increase in parasympathetic activity affect M1, M3 and M3 receptors
no change in M1 or M3 | decrease in neuronal M2 function
38
what happens to eosinophils in asthma
eosinophils cluster around the nerve fibres
39
what do activated eosinophils release
major basic protein (MBP)
40
what does MBP do
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
what is asthma treated. with
anticholinergics
42
actions of anticholinergics
blocks effects of endogenous Ach short and long lasting]competitive inhibitors of M1,2,3 receptors dissociate more slowly from M3
43
outline short term asthma treatment
ipratropium - used in combination with short acting B2-adrenoceptor agonists
44
outline long lasting asthma treatment
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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