4) ANS in the CVS

Question 0

Describe the events between excitation -> contraction?

Answer 0

AP fired -> increase Ca2+ -> Actin and myosin interactions (see ToB)

Question 1

How is the resting membrane potential set?

Answer 1

Via permeability of K+ ions - channels open, K+ leaves the cell down the conc. gradient (small permeability to other ions hence Ek not met)
Na+K+ATPase pump sets the gradients for the membrane potential and only contributes 5-10mV to the potential (electrogenic pump)

Question 2

Describe the ventricle action potential?

Answer 2

1) Open V-gated Na+ channels (increase permeability to Na+) trying to reach ENa = depolarisation
2) K+ channels open briefly -> transient outward K+ current (initial repolarisation -> quick inactivation of these channels
3) Open L-Type Ca2+ v-gated channels (some K+ channels open also)
= PLATEAU - balance between EK and ECa
4) Repolarisation due to inactivation of Ca2+ channels and v-gated K+ channels open - k+ efflux
5) RMP reached with background K+ channels open

Question 3

Describe the action potential sent by SAN pacemaker cells?

Answer 3

1) Unstable RMP - PACEMAKER POTENTIAL (aka funny current) - HCN channels open (via hyperpolarisation) allow Na+ influx
2) Threshold is reached - HCN channels inactivated
3) Ca2+ v-gated channels open - depolarisation upstroke
4) Opening of V-gated K+ channels for repolarisation

Question 4

Importance of cAMP in regards to HCN channels?

Answer 4

cAMP -> PKA -> HCN channels phosphorylated -> operate to allow Na+ to enter
Low cAMP -> less HCN channels operating -> slower depolarisation as pacemaker potential is shallower and slower = Low HR
(Parasympathetic effect - M2 - Gi protein)

Question 5

Properties of the SAN? (2)

Answer 5

1) Sets the rhythm of the heart
2) Depolarises faster - forcing other pacemakers to depolarise quicker e.g AVN or Purkinje have slower automaticity and are overriden. In the absence of SAN - other pacemakers take over

Question 6

Describe histological features of cardiac cell? (4)

Answer 6

1) Intercalated disks join cells at Z lines
2) Gap junctions allow movemet of ions and electrical coupling
3) Single central cell nuclei, striated cells, branched
4) Desmosomes fix cells together

Question 7

How to increase intracellular Ca2+ for cardiac cells?

Answer 7

Depolarisation -> L Type Ca2+ channels open -> Local calcium conc. increases via entry through T tubules -> Opens CICR channels (Ryanodine receptor) in SR -> higher levels of calcium for contraction -> sliding filament theory

Question 8

How to regulate myocyte contraction? (3)

Answer 8

Return Ca2+ resting levels via…

1) SERCA - pump most Ca2+ into the SR (^Ca2+ leads to ^Pumping)
2) NCX
3) PMCA on the sarcolemma

Question 9

Describe histological features of smooth muscle? (3)

Answer 9

1) Not striated, fusiform, criss cross actin and myosin filaments
2) Held by gap junctions for electrical coupling
3) No T tubules

Question 10

Describe the process of smooth muscle cell contraction?

Answer 10

1) Ca2+ enters via L Type Ca2+ channels OR GPCR’s send Gq to send IP3 signal to release Ca2+ from SR
2) 4 Ca2+ molecules bind to 1xCalmodulin -> activates MLCK
3) MLCK phosphorylates myosin head light chain to allow actin interation via the hydrolysis of ATP -> contraction
4) MCLP used to dephosphorylate myosin head light chain -> myosin head inactivated

Question 11

Regulation smooth muscle cell contraction?

Answer 11

MYOSIN head -
^MLCK = ^Phosphorylated myosin head light chain = ^contraction
PKA inhibits MLCK -> inhibits contraction

Question 12

Causes of Hyperkalaemia? (2)

Answer 12

K+ supplements
Renal failure (as the kidneys filter most K+ out of the body)
Beta blockers

Question 13

Describe the process of hyperkalaemia (>5mM extracellularly)?

Answer 13

1) Disrupts conc. gradients - EK is more positive
2) Slower movement of Na+ into the cell as it’s less negative (not such a wide gradient) = depolarisation is slower
3) Slower and less steep pacemaker potential -> aiming to reach threshold
4) Na+ channels open and inactivate within the timespan to reach threshold = less Na+ influx = threshold not met = No AP fired
5) No (or slower) excitation cell to cell - AP’s spread out
6) Lowered HR -> Arrythmia -> Asystole

Question 14

Describe the process of hypokalaemia?

Answer 14

1) Disrupted concentration gradient = EK is more negative
2) Faster movement of Na+ into the cell due to larger gradient difference and more negative in the cell - positive ion is attracted
3) Faster depolarisation due to faster/steeper pacemaker potential - threshold reached quicker
4) Faster excitation from cell to cell and AP’s are fired closer together
5) Increased HR -> Arrythmia -> Tachycardia

Question 15

Causes of hypokalaemia?

Answer 15

B2 agonists

Increases cellular uptake of K+ via the Na+K+pump

Question 16

Describe the features of the ANS?

Answer 16

1) 2 neurones - 1 pre and 1 post ganglion (ganglion = collection of cell bodies)
2) 3 branches - Sympathetic, Parasympathetic, (Enteric)
3) Exerts control over SM, viscera, exocrine glands (involuntary control)

Question 17

Describe features of sympathetic and parasympathetic branches of the ANS?

Answer 17

see ToB

Question 18

Why do different tissues have different adrenoreceptors? (2)

Answer 18

1) Allows for diversity of action

2) Allows for selectivity of drug action

Question 19

Difference between nicotinic and muscarinic receptors?

Answer 19

Nicotinic - Ligand gated ion channel

Muscarinic - GPCR

Question 20

How is noradrenaline released?

Answer 20

Pre ganglion release Ach -> bind to nicotinic receptors of chromaffin cells -> noradrenaline released into the bloodstream

Question 21

ANS action on the heart?

Answer 21

Sympathetic - Positive chronotropic and inotopic (B1 adrenoreceptor)
Parasympathetic - negative chronotropic and lowers AVN conduction velocity (M2 muscarinic receptor)

Question 22

ANS action on the SAN?

Answer 22

Sympathetic - ^cAMP -> ^HCN -> ^pacemaker potential -> ^HR
mediated by B1 adrenoreceptors results in increasing SAN action

Parasympathetic - decreases cAMP -> decreases phosphorylation of HCN -> slows pacemaker potential -> decreases HR and SAN activty
ALSO… Increase K+ conductance, cell RMP more negative, requires higher action of HCN channels to hit threshold but cAMP is limiting

Question 23

3 factors that allow noradrenaline to increase the force of contraction of the heart?

Answer 23

1) Activates B1 adrenoreceptors -> Gs -> ^cAMP -> PKA-> ^Phosphorylation of Ca2+ channels increases Ca2+ influx during the AP = more calcium available to contraction
2) Increased uptake of Ca2+ in SR available for release
3) Increased sensitivity of contractile machinery to Ca2+

Question 24

Define vasomotor tone?

Answer 24

• Constant activity usually to constrict vasculature
• Action of sympathetic output mediated by a1 receptors -> vasoconstriction on arteries, Arterioles, veins
  (Some blood vessels have a1 and b2 receptors to determine vasomotor tone e.g liver, myocardium, skeletal muscle)
• Tone allows for dilatation and increased constriction

Question 26

Effect of increased and decreased sympathetic output on vasomotor tone?

Answer 26

DECREASE sympathetic output -> vasodilation as less NA binds to a1 -> lowers BP
INCREASE sympathetic output -> vasoconstriction as more NA binds to a1 -> increases BP

Question 27

How does the a1 and b2 receptor work?

Answer 27

A1 -> Gq -> +Phosphlipase C -> IP3 ligand binds to receptor-> release calcium from store -> contraction of SM -> vasoconstriction

B2 -> Gs -> +Adenyly Cyclase -> cAMP -> ^PKA -> phosphorylates MLCK (inhibited) -> less contraction = vasodilatation

Question 29

Describe the effects of local metabolites on vasculature?

Answer 29

• H+,K+, Adenosine, ^CO2 Partial pressure produced by active tissues (exercise) = have a vasodilator effect (stronger effect than adrenaline)
• Needed for adequate perfusion of skeletal and coronary muscle

Question 30

ANS control on high and low blood pressure?

Answer 30

1) High pressure Baroreceptors found in the arch of the aorta and the carotid sinus are stretched when there’s high arterial pressure
2) Send input via vagus nerve and glossopharyngeal nerve -> Medulla
3) Medulla determines output and sends down efferent nerve fibres
4) Effect: a) decrease AP firing = decrease HR 2) Increase vasodilation = lowers BP

Low pressure - same mechanism but receptors found in wall of right atrium or in large systemic veins

Question 31

Describe effects of Sympathomimetics (adrenoreceptor agonists)?

Answer 31

• B2 agonist e.g adrenaline used for 1) anaphylactic shock -> vasodilator -> lowers BP 2) restore function in cardiac arrest
• B1 agonist 1) Dobutamine: given in cardiogenic shock 2) Salbutamol: given for asthma to relax bronchial smooth muscle - ^air in

Question 32

Describe effects of adrenoreceptor antagonists?

Answer 32

• A1 antagonist e.g Prazosin used for hypertension as it inhibits NA binding to a1 on smooth muscle vasculature -> vasodilation
• Non selective B1,B2 antagonist e.g Propanolol slows HR and reduced force of contraction (B1) and bronchoconstriction (B2)
• Selective B1 antagonist e.g Atenolol is given to lower HR but prevent risk of bronchoconstriction

Question 33

Describe effects of Cholinergic agonists and antagonists?

Answer 33

• Muscarinic agonists: e.g Pilocarpine treats Glaucoma - activated constrictor papillae muscle to reduce eye pressure
• Muscarinic antagonists: e.g Atropine or Tropicamide used to increase HR and bronchial dilation and dilate pupils (for examination)

Question 34

Effects of circulation adrenaline and noradrenaline on vasculature?

Answer 34

(Adrenaline has a higher affinity for B2 receptors)

• ^Adrenaline bind to b2 receptor = vasodilation
• ^^Adrenaline binds to b2 and a1 receptors = vasoconstriction
• ^Noradrenaline binds to a1 receptors = vasoconstriction

Question 35

ANS action on different organs?

Answer 35

1) Skin- tone is high -> arterio-venous anastomoses and pre capillary sphincters are shut down (open for thermo regulation)
2) Skeletal muscle- tone is high at rest, during exercise vasodilator metabolites decrease tone
3) Gut- tone is low when eating due to vasodilator metabolites produced in gut tissue
4) Brain- tone is constant and not affected by sympathetic output
5) Veins- sympathetic output causes veno-constriction to allow increases blood back to the heart

Question 36

What are the corresponding G proteins and effects for each adrenergic and Cholinergic receptor?

Answer 36

A1 - Gq: + Phospholipase C Q
A2 - Gi: -Adenyly Cyclase I
B1- Gs: +Adenyly Cyclase S
B2 - Gs: +Adenyly Cyclase S

M1- Gq: + Phospholipase C Q
M2 - Gi: -Adenyly Cyclase I
M3 - Gq: + Phospholipase C Q