CVS Session 4 Flashcards Preview

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Flashcards in CVS Session 4 Deck (106):
0

What is the main factor causing establishment of the resting membrane potential?

Potassium permeability of the CSM at rest

1

Which channels in the CSM are open at rest?

Inward rectifier potassium channels

2

Why is the resting membrane potential of a cardiac myocyte -90 mV and not Ek (-95 mV)?

Small permeability of CSM to other ions

3

Between which two equilibrium potentials does the membrane potential of a ventricular myocyte stay within throughout an action potential?

Sodium (+30 mV)
Potassium (-90 mV)

4

How long does a ventricular action potential last?

~280 ms

5

What determines the point of plateau in a ventricular action potential?

Myocyte type

6

What causes the upstroke of a ventricular action potential?

Opening of V-G sodium channels --> sodium influx

7

What two events cause the initial repolarisation of the ventricular action potential?

Transient V-G outward potassium channels --> potassium efflux
Reversal of NCX caused by depolarisation --> small -ve current

8

What causes the plateau of action potential in a ventricular cardiac myocyte?

Opening of V-G L-type calcium channels --> calcium influx balanced w/ potassium efflux

9

What causes repolarisation of the ventricular action potential?

V-G potassium channels --> potassium efflux

10

How do V-G potassium channels vary?

Depend on myocyte present - different types behave differently contributing differently to electrical properties of the myocyte

11

How is the membrane potential of SAN cells described?

Unstable

12

What is the pacemaker potential?

Slow depolarisation to threshold

13

What initiates Ip?

Membrane potential more -ve than -50 mV activating hyperpolarisation-activated cyclic-nucleotide (HCN) gated channels

14

What do HCN channels do?

Allow sodium influx at SAN myocyte membrane potential
Also potassium influx at other potentials

15

How can the activation of the pacemaker potential be increased?

A more -ve membrane potential

16

After threshold has been reached, what causes the upstroke of the SAN action potential?

Opening of V-G calcium channels --> calcium influx

17

What causes the downstroke of the SAN action potential?

Opening of V-G potassium channels --> potassium efflux

18

Why do pacemaker cells not require innervation?

They do not sit at rest so have natural automaticity

19

Why is the SAN the 'master pacemaker'?

It is fastest to depolarise so sets rhythm of contraction

20

What will take over the pacemaker function of the SAN if it is compromised?

AVN

21

How are the action potential graphs of the SAN and AVN related?

Similar shape but AVN is over a longer period of time

22

How are the action potential graphs of atrial muscle, Purkinje fibre and ventricular muscle cells related?

All similar shape w/ resting potential around -80 mV

23

What is the approximate resting membrane potential of the pacemaker cells?

-50 mV

24

What gives cardiac muscle cells mechanical strength?

Glycoprotein that spans membrane and crosses gap b/w cells - desmosome

25

What facilitates electrical coupling of cardiac cells?

Connexon subunits on both sides of membrane forming non-specific pore - gap junction

26

What is the function of intercalated disks?

To join cardiac muscle cells

27

Describe the nucleus in a cardiac muscle cell.

Single
Central

28

What releases 25% of the calcium needed for the sliding filament model in cardiac muscle cells?

Depolarisation opening L-type calcium channels in T-tubules

29

What causes calcium-induced calcium release?

Localised increase in calcium concentration opens CICR channels in sarcoplasmic reticulum

30

Why is there a close link b/w L-type calcium channels and CICR channels in cardiac muscle cells?

Cardiac tissue needs actual calcium influx for contraction

31

What function does calcium perform during contraction of the cardiac muscle cell?

Binds to TnC --> conformational tropomyosin change --> reveals myosin binding site on actin

32

What function does calcium have during diastole?

Increased calcium concentration stimulates SERCA --> calcium moves into SR --> sarcolemmal calcium ATPase and sodium/calcium exchanger pump calcium out of the cell through the CSM

33

How is the tone of BV controlled?

Smooth muscle cells in tunica media of arteries, arterioles and veins

34

How do the actin filaments in myocytes of BV compare to those in other cells?

Longer so can shorten cell more

35

How are actin filaments in BV myocytes anchored within the cell?

Dense bodies
Bonds

36

What can cause excitation-contraction coupling of BV myocytes?

Depolarisation
Activation of GPCRs

37

How does depolarisation cause excitation-contraction coupling?

Allows entry of calcium through calcium channels

38

What class of GPCRs are activated in excitation-contraction coupling?

Alpha-adrenoreceptors

39

Give a brief overview of the activation of GPCRs causing excitation-contraction coupling.

IP3 acts as calcium channel --> SR releases calcium --> calcium binds to calmodulin instead of TnC --> MLCK activated which phosphorylates regulatory light chain on myosin head --> actin-myosin interaction

40

What affect does decreasing calcium levels have on myosin light chain phosphatase?

Causes it to dephosphorylate the myosin light chain --> no interaction --> relaxation

41

What is PKA?

Protein Kinase A - phosphorylates MLCK therefore inhibiting contraction as it prevents it phosphorylating the light chain on myosin head

42

What is PKA regulated by?

cAMP

43

Why does the contraction of a BV myocyte last longer than in other myocytes?

Attachment formed during contraction can become locked

44

What does the ANS exert control over?

Vascular and visceral smooth muscle
Exocrine secretion
Rate and force of contraction of the heart

45

What are enteric neurones usually controlled by?

Sympathetic and parasympathetic nerve fibres

46

Where do parasympathetic neurones synapse?

In ganglia close to target tissue

47

How do the lengths of the pre- and post-ganglionic nerve fibres compare?

Long pre-
Short post-

48

Which neurotransmitter and relative receptor do parasympathetic post-ganglionic neurones usually use

ACh
Muscarinic

49

What is the exception to the usual rule of sympathetic post-ganglionic neurones being noradrenergic?

Sweat glands using ACh and muscarinic receptors

50

Where do sympathetic neurones synapse?

Mostly in paravertebral chain but can travel up or down chain before synapsing

51

How do preganglionic neurones of both sympathetic and parasympathetic divisions transmit action potentials?

Release ACh --> binds to nicotinic receptors on post-ganglionic cell --> opens ion channel --> influx of sodium --> depolarisation --> AP down neurone

52

How are chromaffin cells like specialised post-ganglionic symoathetic neurones?

ACh from the preganglionic neurone acts directly on the cell to release adrenaline directly into the bloodstream

53

What do NA and adrenaline act on?

GPCRs with no integral ion channel - adrenoreceptors

54

What allows for diversity and selectivity of drug action at adrenoreceptors?

Different tissues have different subtypes

55

How do parasympathetic postganglionic neurones transmit action potentials?

Release ACh --> binds to muscarinic receptors on effector cells (GPCRs)

56

What two methods of action can be used to treat asthma?

Stimulate beta-2
Inhibit M3

57

What are the sympathetic and parasympathetic effects on the pupil of the eye and their relevant receptors?

S - dilation (contract radial muscle); alpha-1
P - contraction (contracts sphincter muscle; M3

58

What are the sympathetic and parasympathetic effects on the airways of the lungs and their relevant receptors?

S - relax; beta-2
P - contract; M3

59

What are the sympathetic and parasympathetic effects on the heart and their relevant receptors?

S - increase rate and force of contraction; beta-1
P - decrease rate; M2

60

What are the sympathetic and parasympathetic effects on sweat glands and their relevant receptors?

S - localised secretion; alpha-1
S - generalised secretion; M3
P - no effect

61

Why does increased sympathetic activity to the heart not have to increase activity elsewhere?

Drive to different tissues is independent and is only coordinated when needed, e.g. fight or flight

62

Does the ANS initiate electrical activity in the heart?

Nope

63

Which preganglionic fibres transmit the parasympathetic input to the heart?

X cranial nerve - vagus nerve

64

Where does the vagus nerve synapse?

W/postganglionic cells on epicardial surface
W/in walls of heart at SAN and AVN

65

Why does parasympathetic input to the heart not really affect force of contraction?

Doesn't synapse much w/postganglionic cells in ventricles

66

What affect does the binding of ACh released from postganglionic cells to M2 receptors have in parasympathetic innervation of the heart?

-ve chronotropic effect
Decreased AVN conduction velocity

67

How does the sympathetic division innervate the heart?

Long postganglionic fibres from the sympathetic trunk innervate the SAN, AVN and myocardium --> release NA

68

What does binding of NA to beta-1 adrenoreceptors cause in the sympathetic input to the heart?

+ve chronotropic effect
+ve inotropic effect

69

What must be altered to alter pacemaker cell contraction rate?

Slow depolarising pacemaker potential

70

What assists the HCN channels in the action of the funny current?

T-type sodium channels

71

How does the sympathetic branch of the ANS act on pacemaker potentials?

Activates beta-1 receptors --> G-alpha-S activated --> stimulates adenylate cyclase --> increases cAMP --> speeds up pacemaker potential

72

How does the parasympathetic branch of the ANS effect the pacemaker potential?

Activates M2 receptors --> G-alpha-1 activated --> inhibits adenylate cyclase --> decreases cAMP --> increases potassium conductance --> slows down pacemaker potential

73

How does NA increase the force of contraction of the heart?

Beta-1 receptors activated --> increased cAMP --> PKA activated --> calcium channels activated so more calcium during action potential --> more SR calcium uptake so more CICR and increased sensitivity of contractile machinery to calcium

74

What is the exception to the general rule that most BV receive sympathetic innervation?

Erectile tissue

75

What class of receptors is present in most arteries and veins and is abundant in arterioles?

Alpha 1-adrenoreceptors

76

What class of receptors are found in coronary and skeletal muscle vasculature as well as alpha 1-adrenoreceptors?

Beta 2-adrenoreceptors

77

How does varying the sympathetic output to vasculature alter the vasomotor tone?

Decrease = vasodilation
Normal = vasomotor tone
Increase = vasoconstriction

78

What is needed in vasculature in order for there to be constriction?

Basal level of contraction

79

What is the effect of NA and circulating adrenaline in BV w/alpha 1 and beta 2-adrenoreceptors?

NA - contraction
Adrenaline - vasodilatation

80

How does adrenaline cause vasodilatation at physiological concentration?

Higher affinity for beta 2-adrenoreceptors --> increases cAMP --> activates PKA --> opens potassium channels and inhibits MLCK --> relaxation of smooth muscle

81

How can adrenaline cause vasoconstriction at pharmacological concentrations?

Activates alpha 1-adrenoreceptors --> activates G-alpha-Q --> stimulates IP3 production --> increased calcium concentration from stores and influx --> smooth muscle contracts

82

What has a stronger vasodilatation effect than activation of beta 2-adrenoreceptors?

Local metabolites

83

Give some examples of local metabolites.

Adenosine
Potassium
Hydrogen ions
p(carbon dioxide)

84

What is more important for ensuring adequate perfusion of skeletal and coronary muscle than activating beta 2-adrenoreceptors?

Local metabolites

85

What communicates changes in the state of the CVS to the brain?

Afferent nerves

86

What are baroreceptors?

Nerve endings in carotid sinus and aortic arch sensitive to stretch

87

Which two types of receptors detect low pressure and high pressure system changes in BP and alter activity of efferent nerves as a result?

High pressure side - baroreceptors
Low pressure side - atrial receptors

88

What is the baroreceptors reflex?

Increase mean arterial pressure detected by baroreceptors, communicated by afferent pathway to medulla --> coordinates efferent pathways in heart and vessels to cause bradycardia and vasodilatation

89

Which nerves do afferent fibres travel up?

Vagus
Glossopharyngeal

90

What three types of drugs are used which act on the ANS?

Sympathomimetics
Adrenoreceptor antagonists
Cholinergics

91

What two types of molecule make up the sympathomimetic class of drugs?

Alpha-adrenoreceptor agonists
Beta-adrenoreceptor agonists

92

What do sympathomimetics mimic?

Sympathetic nervous system

93

Name three examples of sympathomimetics.

Adrenaline
Dobutamine
Salbutamol

94

How is adrenaline used to treat cardiac arrest and anaphylactic shock?

Cardiac arrest - vasoconstriction to maintain BP
Anaphylactic shock - stimulates alpha 1 receptors to counteract widespread vasodilatation

95

What method of action does Dobutamine follow?

Beta 1-agonist given in cardiogenic shock (pump failure)

96

How does salbutamol work?

Beta 2- agonist specific to airway of lungs to cause dilation, doesn't increase HR

97

Name three examples of adrenoreceptor antagonists.

Prazonin
Propranolol
Atenolol

98

How does prazonin work?

Alpha 1-antagonist --> inhibits NA action on vascular smooth muscle --> vasodilation --> antihypertensive

99

How does propranolol work?

Non beta1/2 selective adrenoreceptor antagonist which acts at beta 1 to slow heart rate and force of contraction and at beta 2 to cause bronchoconstriction

100

How does atenolol work?

Selective beta 1-antagonist given after MI to reduce cardiac workload with less risk of bronchoconstriction

101

Give three examples of Cholinergics.

Pilocarpine
Atropine
Tropicamide

102

How does pilocarpine work?

Muscarinic agonist which acts on constrictor pupillae muscle to treat glaucoma

103

How do atropine and Tropicamide work?

Muscarinic antagonists which increase heart rate and bronchial dilation
Can be used to dilate pupils for eye examination

104

How is the heart normally controlled?

Vagal control w/parasympathetic dominated control

105

What happens if you pharmacologically block the autonomic control to the heart?

Rate increases towards intrinsic heart rate = 100 bpm