Lecture 7: Cardiac Ionotropy

Question 1

Define ionotropy:

Answer 1

The force of contraction of the heart

Question 2

Sympathetic stimulation ___________ cardiac contractility

Answer 2

Increases

Question 3

At rest the heart is under ___________ tone

Answer 3

Sympathetic tone

Question 4

__________________ stimulation has very little effect on the contractility

Answer 4

Parasympathetic

Question 5

How does venous return affect contractility of the heart?

Answer 5

Intrinsic regulator

Increase VR => increases contractility

Question 6

What is an ionotropic agent?

Answer 6

An agent that alters the force produced at the same load

Question 7

Give examples of positive ionotropic agent:

Answer 7

NA/Adr act on β-adrenergics
Digitalis
Increases extracellular Ca

Question 8

NA and Adr cause and increase in cytosolic ____

Answer 8

Calcium concentration

Question 9

Briefly outline the process of excitation-contraction coupling in Cardia muscle:

Answer 9

1. Ca enters the cell via L-type Ca channels when depolarised
2. Ca activates RyR channels on the SR and causes calcium induced calcium release
3. Ca binds to troponin and shifts tropomyosin allowing cross-bridge cycling
4. SERCA pumps Ca back into the SR and a Na/Ca anti-port pumps 3 Na in and 1 Ca out

Question 10

Outline the process by which β-adrenergic stimulation cause ionotropy?

Answer 10

1. NA activates a Gs coupled β-receptor which causes cAMP synthesis by activating adenylate cyclase
2. cAMP activates PKA which phosphorylates L-type channels and increases their opening probability = increased Ca influx
3. PKA indirectly phosphorylates SERCA and increases its pump rate = more Ca stored in the SR for contraction

Question 11

How does acetylcholine exert a negative ionotropic effect?

Answer 11

ACh acts via a Gi linked M2 muscarinic receptor which causes inhibition of adenylate cyclase = decrease in PKA activity

Question 12

Digitalis is a potent __________ ionotropic drug. It’s side effects include ________ and _________

Answer 12

Positive

Arrhythmia and toxic Ca loading

Question 13

How does digitalis work?

Answer 13

Inhibits the Na/K pump and .’. Indirectly affects the Na/Ca anti-port. This increases the [Na]in which produces ionotropy.

Question 14

Why does a high [Na]in cause ionotropy?

Answer 14

Ca efflux via the Na/Ca anti-port is powered by the diffusion gradient for Na. Increased [Na]in decreases the gradient and therefore decreases Ca efflux. The excess Ca is instead pumped into the SR via SERCA .’. More Ca for next contraction.

Cell also becomes hypopolarised from the elevated Na and loss of K