cardio and renal L3

Question 1

______ increase the rate of production of pacemaker potentials, _____ reduces the rate.

Answer 1

Catecholamines increase the rate of production of pacemaker potentials, acetylcholine reduces the rate.

Question 2

how do catecholamines increase the rate of AP in nodal cells?

Answer 2

ß-adrenergic receptors lead to a rise in intracellular cAMP

Question 3

how does ACh decrease the rate of AP firing

Answer 3

M2 muscarinic receptors lower it

Question 4

There are ______ receptors on the nodal cells and on the ventricular cells. The _______ receptors are mainly confined to the nodes.

Answer 4

There are ß1 adrenergic receptors on the nodal cells and on the ventricular cells. The muscarinic receptors are mainly confined to the nodes.

Question 5

how do catecholamines affec thte ca2+ current?

is this imporatn only in the nodal cels?

Answer 5

Increased ICa-L and ICa-T.

Like other effects of catecholamines this is mediated by cAMP

This is important not only in the pacemaker potential, but also in the bulk of the myocardium it enhances Ca2+ entry into cells and thus intensifies strength of contraction

Question 6

the effect of catecholamines can be produced by administration of what? (3)

and blocked by what? (2)

Answer 6

The effect can be mimicked by administration of adrenaline, noradrenaline or isoprenaline and can be blocked by the non specific ß-antagonist propranolol or the ß1 antagonist atenolol.

Question 7

The ß1 receptor in the heart is coupled to the ,……., and thus is linked to a rise in cAMP.

Answer 7

The ß1 receptor is coupled to the G_s G-protein, and thus is linked to a rise in cAMP.

Question 8

The introduction of the ______ leads to an increased likelihood of opening of the channel (L-type Ca2+ cahnnels), which is again reflected by the mean current.

Answer 8

The introduction of the cAMP leads to an increased likelihood of opening of the channel, which is again reflected by the mean current.

Question 9

The time-course of the effect of stimulation of Ca2+ currents by ß1 receptor agonists or by addition of cAMP is quite _____.

Answer 9

The time-course of the effect of stimulation of Ca2+ currents by ß1 receptor agonists or by addition of cAMP is quite slow.

Question 10

The time-course of the effect of stimulation of Ca2+ currents by ß1 receptor agonists or by addition of cAMP is quite slow.

why is it so slow?

Answer 10

• The channel is phosphorylated by cAMP-dependent protein kinase (PKA) so the whole process involves production of cAMP and the consequent stimulation of PKA.
• It is thus much slower than, say, activation of ligand-gated ion channels.
• Reversal of the effect is also rather slow.
• It is possible to mimic the effect of ß1 stimulation by using cholera toxin (which stimulates the G-protein) or by using forskolin (which stimulates adenylyl cyclase).

Question 11

describe how catecholamines can affect ryanodine receptors in the heart

Answer 11

􏰖 Sensitisation of ryanodine receptor channels, so…

􏰖 Ca2+ channels are activated by catecholamines

􏰖 More Ca2+ enters the cell during the plateau phase

􏰖 This leads to activation of ryanodine receptors and release of intracellular Ca2+ stores

􏰖 This produces an additional extra stimulus for muscle contraction and thus produces an increased force of contraction

Question 12

catecholamines effect on the heart

PKA phosphorylates SERCA2 and phospholamban (this is of significance in_________).

Answer 12

PKA phosphorylates SERCA2 and phospholamban (this is of significance in heart failure - see below).

Question 13

describe how catecholamines affect the funny current?

Answer 13

The potential at which If is activated is shifted to more positive levels by catecholamines.

This means that the pacemaker produces more frequent action potentials and a positive chronotropic effect.

Question 14

how do catecholamines affect the delayed rectifier currents in the heart/

Answer 14

The various delayed-rectifier K+ currents producing repolarisation are enhanced, leading to a shortened action potential duration.

This again leads to a positive chronotropic effect.

Question 15

M2 muscarinic receptors are coupled to the ….

Answer 15

M2 muscarinic receptors are coupled to the Gi/o G-protein

Question 16

does ACh affect rate or strength of cantraction more?

why?

Answer 16

The receptors are found mainly in the nodal tissue so cholinergic effects on rate of contraction are greater than those on strength

Question 17

do M2 receptors have the opposite effect of beta adrenergic stimuation?

Answer 17

M2 muscarinic receptors inhibit the formation of cAMP (beta stimuates its production) .

It is therefore not surprising that their stimulation has the reverse effects of catecholamines, and undue activation of M2 receptors (by unusually excessive vagal stimulation) can actually stop the heart.

Question 18

effect M2 stimualtion has on nodal cells?

Answer 18

• Nodal Ca2+ currents are diminished
• The potential at which If is activated is shifted to more negative levels
• The pacemaker produces more widely- spaced action potentials
• IK-ACh is stimulated,hyperpolarising the cells, making it more difficult to produce action potentials

Question 19

wy dont M2 receptors have much influence over the ventricles?

Answer 19

M2 receptors are largely confined to the nodal tissue and do not have much influence on ventricular cells.

Question 20

ACh stimulates the I_K-ATP current.

what effect does this have?

Answer 20

I_K-ACh is a current which is influenced directly by M2 receptor stimulation. Its stimulation hyperpolarises the cell, making it more difficult to elicit action potentials.

Question 21

in the heart which is the dominant nodal tissue?

Answer 21

The sinoatrial node (SAN) is the dominant nodal tissue

Question 22

why is the SA node dominant>

Answer 22

The reason that the sinoatrial node is dominant is that the sinoatrial node discharge is at a higher frequency than the other areas of pacemaker tissue.

Question 23

Discharge rates:

SA node: ___

AV node: ___

Bundle of His: ___

Purkinje fibres: ___

Answer 23

SA node: 70

AV node: 60

Bundle of His: 50

Purkinje fibres: 40

Question 24

Any pacemaker at a site other then the sinoatrial node is called an ….

Answer 24

Any pacemaker at a site other then the sinoatrial node is called an ectopic pacemaker or an ectopic focus.

Question 25

how are impiulses conducted correctly through the myocardium?

Answer 25

Normally, the impulse is directed in the right direction because of inactivation of ion channels making tissue refractory

Question 26

MI effects on the myocardium conductive pathways

Answer 26

Myocardial infarction/damage destroys heart muscle in an arbitrary manner and can thus compromise the conductive pathways

Question 27

can MI lead to dysrhythmias?

Answer 27

yep

Question 28

Cardiac muscle can conduct in ehich direction?

Answer 28

Cardiac muscle can conduct in any direction (as it is a functional syncytium)

Question 29

in MI - the dead cardiocytes are replaced by what?

Answer 29

The tissue is destroyed, and is ultimately replaced by connective tissue which is non-conductive

Question 30

describe Wolff-Parkinson-White syndrome’

Answer 30

some people have congenital abnormal (extra) conducting fibres which accelerate the transmission of the impulse from atria to ventricles.

The condition is called ‘Wolff-Parkinson-White syndrome’.

Question 31

t or f

Dysrhythmias can arise as a result of mutant ion channels

Answer 31

T -

eg long QT syndrome

Question 32

describe re-entrant dysrhythmia

Answer 32

when tissue is damaged, conduction is compromised, producing inappropriate excitation and/or reentry or circus movements.

damaged tissue may conduct more slowly

Question 33

what is the Vaughan williams classificaiton of antidysrhythmic drugs based on?

Answer 33

the classification is based upon the effect of the drugs on the action potential and not on the type of drug itself

Question 34

describe class 1 antidysrhythmic drugs

Answer 34

block Na channels

Question 35

how are class 1 antidysrhythmic drugs subdivided?

Answer 35

• IA Increased action potential duration, with an intermediate rate of association/dissociation. Examples of drugs are quinidine and procainamide
• IB Decreased action potential duration, with very fast association and dissociation. Example: lidocaine
• IC No effect on action potential, but very slow association and dissociation. Example: flecainide

Question 36

describe class 2 antidysrhythmic agents

Answer 36

Sympathetic antagonists (i.e. ß-blockers). Examples: propranolol, atenolol

Question 37

describe class 3 antidysrhythmic drugs

Answer 37

These drugs prolong the action potential and thus also the refractory period.

The best known example is amiodarone

Question 38

describe class 4 antidysrhythmic drugs

Answer 38

These are Ca2+-channel blockers which reduce thus Ca2+ entry. The most commonly used is verapamil

Question 39

give class 1a antidysrhythmic drug examples

Answer 39

quinidine and procainamide

Question 40

give a class 1b exmaple?

Answer 40

lidocaine

Question 41

give a class 1C exmaple

Answer 41

flecainide

Question 42

give two class 2 exmaples

Answer 42

propranolol, atenolol

Question 43

give a class 3 example

Answer 43

amiodarone

Question 44

give a class 4 exmaple

Answer 44

verapamil

Question 45

T or F:

There is enhanced sympathetic activity during myocardial infarction

Answer 45

T

its why beta blockers work well

Question 46

more details about class 3 antidysrhythmic drugs

Answer 46

• The only significant drug in this group is amiodarone
• Its mode of action is complex but it prolongs the action potential and thus
• the refractory period
• Under differing conditions it can block both inward (Na+) and outward (K+) currents
• It is used for ventricular dysrhythmias and re-entrant dysrhythmias that do not respond to Class I drugs

Question 47

diltiazem belpongs to whcih class of antidysrhythmics?

Answer 47

class 4

Question 48

fat

Answer 48

mamba