Lecture 18: Ionic basis of cardiovascular control

Question 1

What comprises the intrinsic regulation of the cardiac muscle contraction?

Answer 1

Frank-Starling relationship

Increased contractility

Longer and stronger

“More crossbridges means more of everything”

Question 2

What comprises the extrinsic regulation of the cardiac muscle contraction?

Answer 2

Sympathetic stimulation

Faster and stronger

NOT longer duration

“Extant crossbridges work harder and faster”

Question 3

What is the natural rate of an isolated or denervated heart?

Answer 3

100bpm

Question 4

What determines heart rate?

Answer 4

Slope of the pacemaker potential

Question 5

What is the effect of noradrenaline (sympathetic) on the If channel?

Answer 5

Increases activity - net inward current

Increases slope of the pacemaker potential (increases rate)

Acts on Beta1 receptors

Question 6

What is the effect of noradrenaline (sympathetic) on the Ca channels?

Answer 6

Increases force of contraction

Question 7

What is the effect of noradrenaline (sympathetic) on the delayed rectifier K channels?

Answer 7

Shortens AP duration

Faster heart rate

Question 8

What is the HCN channel?

Answer 8

Non-specific monovalent cation channel

Opens when the membrane gets more negative

Question 9

What is the effect of sympathetic activity of If?

Answer 9

Increases If

Question 10

What is the reverse potential of If?

Answer 10

-10mV

Question 11

What pathway is activated by Gq?

Answer 11

PLC - IP3 - DAG
Ca

Vasoconstriction in most organs

Question 12

What pathway is activated by Gs?

Answer 12

Adenylate cyclase - cAMP

Increase contractility, HR, perfusion of skeletal muscles, lipolysis in adipose tissue

Question 13

What pathway is deactivated by Gi?

Answer 13

Adenylate cyclase - cAMP

Less insulin, more glucagon

Question 14

What is the effect of acetylcholine on heart rate?

Answer 14

Vagal - parasympathetic

Increases K current so hyper polarises the membrane

Decreases the slope of the pacemaker potential

Slows HR

Question 15

What is atropine?

Answer 15

Blocker of muscarinic receptor - blocks vagal slowing of HR

So increases HR

Question 16

When do the inward rectifier K+ channels open?

Answer 16

When the voltage goes below -60mV

Question 17

During the AHP which channels are open?

Answer 17

Delayed rectifiers and inward rectifiers are open

Almost all Na channels are inactivated

Question 18

What is the refractory period?

Answer 18

When there is so much positive current leaving the cell, it is impossible to depolarise it again

Question 19

At what stage are the delayed rectifier channels closed?

Answer 19

When the membrane is at rest

Question 20

What is the effective refractory period (ERF)?

Answer 20

When it becomes nearly impossible to start a new action potential

In cardiomyocyte, lasts for duration of AP

Protects the heart from unwanted extra action potentials between SA node initiated heart beats

Question 21

What are T-tubules?

Answer 21

Invaginations of plasma membrane into myocyte

T tubule depolarises –> terminal Cisterna detects it –> terminal cisterna sends it throughout SR

Question 22

What is the terminal cisternae?

Answer 22

Enlarged area of SR

Specialised for storing and releasing calcium

Question 23

What is excitation-contraction coupling?

Answer 23

The link (molecular process) between the depolarisation of the membrane (with a tiny influx of calcium) and the consequent huge increase cytosolic calcium that then leads to contraction

Question 24

What is the primary control of cardiac muscle contraction?

Answer 24

Diffusion of free calcium into the cytoplasm

Question 25

Where are large concentrations of calcium stored in the skeletal muscle?

Answer 25

Sarcoplasmic reticulum

Question 26

What is the name of the receptor on the terminal cisterna that allows the release of large amounts of calcium?

Answer 26

Ryanodine receptors

Question 27

What is the name of the receptor in the cell membrane that allows a small influx of calcium into the cell to activate the RyR?

Answer 27

DHPR

Question 28

What is the role of SERCA?

Answer 28

In the SR membrane - pumps calcium back into the SR Requires ATP

Question 29

What is the effect of sympathetic stimulation of the EC coupling?

Answer 29

Increases EC coupling

Question 30

What may be caused by calcium overload?

Answer 30

Risk of ectopic beats and arrhythmia

Question 31

What is the effect of a DHP calcium channel blocker.

Answer 31

Vasodilates - opposes hypertension Amlodipine

Question 32

What is the effect of non-DHP calcium channel blockers?

Answer 32

Anti-anginal and anti-arrhythmic BUT makes heart failure worse Verapamil - anti arrhythmic (blocks heart vessels) Diltazem - anti-anginal and anti arrhythmic (blocks hear and vessel channels)

Question 33

What is digoxin?

Answer 33

Positive inotropic agent - increases stroke volume and contractility Works by inhibiting Na/K pump - causes increased Ca in the cytosol Also stimulates vagus - slows HR Used for AF

Question 34

What is the effect of beta2 stimulation on VSMCs in peripheral skeletal muscles?

Answer 34

Cause VSMC relaxation B2 - cAMP - PKA - p-MLCK (inactive when phosphorylated) - can't phosphorylate or activate myosin

Question 35

What is the effect of alpha1 stimulation on VSMCs in core organs and GI tract?

Answer 35

Smooth muscle contraction A1 - PLC - IP3 - Ca - CaM - MLCK (activate when bound to Ca-CaM) - p-myosin

Question 36

What is bradykinin?

Answer 36

Peptide hormone that loosens capillaries and blood vessels Vasodilator - stimulates NO production in endothelium Increases capillary permeability - increases saliva production

Question 37

What is the effect of ACE inhibitors on bradykinin?

Answer 37

ACE inhibitors prevent degradation of bradykinin - causes dry cough

Question 38

When is creatinine kinase released from myocytes?

Answer 38

During necrosis

Question 39

When is CRP released?

Answer 39

Increased in response to inflammation

Question 40

When is troponin released from cardiomyocytes?

Answer 40

During necrosis - elevated during AMI but not during unstable angina