CVS Session 4 Flashcards
0
Q
Which channels in the CSM are open at rest?
A
Inward rectifier potassium channels
1
Q
What is the main factor causing establishment of the resting membrane potential?
A
Potassium permeability of the CSM at rest
2
Q
Why is the resting membrane potential of a cardiac myocyte -90 mV and not Ek (-95 mV)?
A
Small permeability of CSM to other ions
3
Q
Between which two equilibrium potentials does the membrane potential of a ventricular myocyte stay within throughout an action potential?
A
Sodium (+30 mV)
Potassium (-90 mV)
4
Q
How long does a ventricular action potential last?
A
~280 ms
5
Q
What determines the point of plateau in a ventricular action potential?
A
Myocyte type
6
Q
What causes the upstroke of a ventricular action potential?
A
Opening of V-G sodium channels –> sodium influx
7
Q
What two events cause the initial repolarisation of the ventricular action potential?
A
Transient V-G outward potassium channels –> potassium efflux
Reversal of NCX caused by depolarisation –> small -ve current
8
Q
What causes the plateau of action potential in a ventricular cardiac myocyte?
A
Opening of V-G L-type calcium channels –> calcium influx balanced w/ potassium efflux
9
Q
What causes repolarisation of the ventricular action potential?
A
V-G potassium channels –> potassium efflux
10
Q
How do V-G potassium channels vary?
A
Depend on myocyte present - different types behave differently contributing differently to electrical properties of the myocyte
11
Q
How is the membrane potential of SAN cells described?
A
Unstable
12
Q
What is the pacemaker potential?
A
Slow depolarisation to threshold
13
Q
What initiates Ip?
A
Membrane potential more -ve than -50 mV activating hyperpolarisation-activated cyclic-nucleotide (HCN) gated channels
14
Q
What do HCN channels do?
A
Allow sodium influx at SAN myocyte membrane potential
Also potassium influx at other potentials
15
Q
How can the activation of the pacemaker potential be increased?
A
A more -ve membrane potential
16
Q
After threshold has been reached, what causes the upstroke of the SAN action potential?
A
Opening of V-G calcium channels –> calcium influx
17
Q
What causes the downstroke of the SAN action potential?
A
Opening of V-G potassium channels –> potassium efflux
18
Q
Why do pacemaker cells not require innervation?
A
They do not sit at rest so have natural automaticity
19
Q
Why is the SAN the ‘master pacemaker’?
A
It is fastest to depolarise so sets rhythm of contraction
20
Q
What will take over the pacemaker function of the SAN if it is compromised?
A
AVN
21
Q
How are the action potential graphs of the SAN and AVN related?
A
Similar shape but AVN is over a longer period of time
22
Q
How are the action potential graphs of atrial muscle, Purkinje fibre and ventricular muscle cells related?
A
All similar shape w/ resting potential around -80 mV
23
Q
What is the approximate resting membrane potential of the pacemaker cells?
A
-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
