Autonomic control of cardiac output

Question 1

What two subbranches of the ANS produce opposing effect on CO and what are these effects?

Answer 1

Parasympathetic - decrease CO

Sympathetic - increase CO

Question 2

What is the organisation sympathetic input?

Answer 2

Sympathetic chain T1-T4, post ganglionic neurone releases noradrenaline.

Question 3

What is the organisation of parasymathetic input?

Answer 3

Vagus (X) innervates the heart, postganglionic neurone releases acetylcholine

Question 4

What receptors are involved in sympathetic response?

Answer 4

Adrenergic (B1, A2)

Question 5

What receptors are involved in parasympathetic response?

Answer 5

Muscarinic (M2)

Question 6

What factors does the ANS affect?

Answer 6

Heart rate - chronotropy

Stroke volume - Inotropy (force) for a given fibre length

Question 7

How is heart rate increased (linking to the action potential)?

Answer 7

APs fire more frequently - Increased rate of pacemaker potential decay

Question 8

How is contractility increased (linking to the action potential)?

Answer 8

Maintaining high [Ca2+] in ventricular myocytes

Question 9

How is chronotropy increased through sympathetic input?

Answer 9

Increased concentration of cAMP interacts with the if HCN channels in the sinoatrial node to increase their open state probability, this increases the if (funny current) which accelerates the rate of pacemaker potential decay, producing a positive chronotropic effect.

cAMP also activates protein kinase A which phosphorylates the L-type calcium channels to increase their open state duration and so activated at more -ve Em. In SAN myocytes, this accelerates pacemaker potential decay, resulting in positive chronotropy,

Protein kinase A also phosphorylates the delayed rectifier K+ channels resulting in an increase in the repolarising outward current acting to shorten the ventricular action potential

Question 10

What happens when noradrenaline binds to B1 receptors?

Answer 10

Beta 1 adrenoreceptors (Gs coupled) are present in the cardiac cell membrane. When noradrenaline or adrenaline binds to the receptor, G unit activates adenylate cyclase. In its active form, adenylate cyclase catalyses the conversion of ATP into cAMP.

Question 11

How is ionotropy increased with sympathetic input?

Answer 11

cAMP also activates protein kinase A which phosphorylates the L-type calcium channels to increase their open state duration and so activated at more -ve Em. in ventricular and atrial myocytes this increases intracellular calcium increases the Ca2+ plateau phase of their action potential exhibiting a positive inotropic effect.

PKA also phosphorylates phospholamban, deactivating its usual function as a SERCA pump inhibitor on the sarcoplasmic reticulum (SR) in cardiac myocytes. Due to this, more calcium enters the SR and is therefore available for the next contraction so each contraction is positively inotropic

Question 12

What happens when acetylcholine binds to M2 receptors?

Answer 12

M2 muscarinic receptors on SAN cells (Gi protein coupled)

Decrease cAMP, sympathetic effects don’t occur thus, less steep gradient of pacemaker potential.

Ultimately, less phosphorylation of L-type Ca2+ channels results in their decreased open probability and longer duration to reach threshold.

The beta subunit activates inward rectifier potassium channels causing an increase in outward K+ causing hyperpolarisation so Em approaches threshold more slowly.

Deceleration of pacemaker potential decay slope leading to a negative chronotropic effect.