Basic Electrophysiology

Question 1

How does elictrical conduction travel through the heart?

Answer 1

• Begins with actionpotential initiated at the SA node
• conductied from SA to Atrial muscle
• Spread through atria to the AV node where conduction slows
• Action potentials travel rapidly through the conduction system to the apex of the heart
• Action Potentials spread upward through the ventricular muscle
• eventually the entire heart returns to the resting state remaining there until another action potential is generated in the SA node

**AV initiated delay allows the ventricle to fill

Question 2

How are action potentials in the SA and AV nodes different from action potentials everywhere else?

Answer 2

they have a slower upstroke! (depolarization)

Question 3

WHat are the 6 steps of electrical conduction in the heart and how do these relate to ECG?

Answer 3

1. Atrial depolarization initiated by the SA node causes the (P wave)
2. WIth atrial depolarization complete the impulse is delayed at the AV node (delay between P and Q)
3. Ventricular depolarization begins at apex, causing the QRS complex, Atrial repolarization ocntinues
4. Ventricular depolarization is complete (space between S and T)
5. Ventricular repolarization begins at apex, causing the T wave
6. Ventricular repolarization is complete

Question 4

Describe the very basics of depolarization and repolarization in cardiac ventircular myocytes

Answer 4

Na rushes in

Ca channels open keeping the cell positive

K channel opens cell becomes more negative

Question 5

Is there only 1 K channel? WHat are the basic kinetics of NA, Ca and K channels?

Answer 5

no and they all have differnet kinetic properties, some are slower than others

Na fast, Ca a little slower, K even slower

Question 6

Where are a majority of the Na, Ca and K ions found?

Answer 6

Na extracellular (140mM)

K intracellular (140mM)

Ca extracellular (2.4mM)

Question 7

What is ionic equilibrium?

Answer 7

the process of ions diffusing and chaging the membrane voltage will continue until the membran potential attains a value sufficient to balance the ion concentration gradient and then the ion will be in equilibrium

Equilibrium Potential:

Electrical Forces=chemical forces there is no net flux

Question 8

What is equilibrium potential and how do we calculate it?

Answer 8

Equilibrium potential is when electrical forces=chemical forces and there is no net flux

It is calculated via Nerst Equation

an ion of valence z will be in equilibrium at the Nernst potential

*****used when there is only one ion channel open even if there are mutliple different ions in the cell****

Question 9

WHat do we use if there is more than one type of ion channel permeable?

Answer 9

the membrane voltage will be between K and Na

Goldman-Hodgkin-Katz equation

Question 10

What is Ohm’s law?

Answer 10

V= I*R

when you are at RMP V=0

when you put in a K channel V= -90

Question 11

WHy is RMP not -90?

Answer 11

at rest cell is most permeable to K so it has the most influence

But there is also leakage of Na into the cell via leak channels

Na/K pump maintains the ionic gradients

(Note K flows out of the cell making the cell more negative, and Na flows into the cell making the cell more positive)

Question 12

What are the exchngers and active transporters essential for maintaining ionic gradients?

Answer 12

Na/K ATPase: Na and K both against gradient (3na out, 2K in) ATP

Na-Ca Exchanger: forward=Ca out of the cell Na in using the Na’s gradient for NRG, reverse=Ca in Na out

Ca-ATPase: Ca pump out of cell uses ATP

SERCA: Sarco/endoplasmic reticulum Ca ATPase. returns Ca into SR ATP (requires phosphorylation/separation of phospholambin to be active)

Question 13

WHat is the difference in action potential beteen a ventricular myocyte and SA node?

Answer 13

• Ventricular myocyte: Fast cell response=fast depolarization
  
  • phase 0: I_Na depolarization phase
  • Phase 1: I_{TO(K channel for early repolarization)}
  • Phase 2: Plateau Phase: delicate balance/ easily perturbed between Ca, Na/Ca, K channels
  • Phase 3: Repolarization phase (K channels)
  • Phase 4: resting state (I_K and I_{f) remember f=Na slow leak channel}
• SA Node:
  
  • phase 0: depolarization
  • phase 3: repolarization
  • phase 4: rest

***SO: the SA node does not has an early repolarization phase or a plateau phase! but the ventricular myocyte does!

Question 14

What is:

PR interval

PR segment

ST segment

QT interval

QRD complex

RR interval

Answer 14

PR interval: measure of time from the start of atrial depolarization to the start of venticular depolarization

PR segment: measure of time from the end of atrial depolarization to the start of ventricular depolarization

ST segment: time from the end of ventricular depolarization to the start of ventricular repolarization

QT interval: ttime from the beginning of ventricular depolarization to the end of ventricular repolarization

QRS complex: measure duration of ventricular action potential

RR interval: measure time between beats

RR interval

Question 15

Long QT syndrome is a channelopathy, what is long QT syndrome?

Answer 15

a block or dysfunction of K channels delay the repolarization of the cardiac action potential which means a longer depolarization (QT).

In addition upregulation of Na or Ca current can also lead to a delay in repolarization since the cardiomyocytes will stay depolarized longer

this is bad bc some Na channels might undergo another depolarization while this depolarization is occuring bc enough time has passed that it is out of the refractory period (in order for depolarization to occur again you need time and being less negative)

This leads to torsades de pointes which is ventricular tachycardia that can lead to sudden cardiac death

Question 16

What are the 2 major repolarizing current and are are genetic abnormalities associated with them?

Answer 16

LQT1 (IKs) and LQT2 (IKr)

inherited long QT is associated with these 2 channels

Question 17

A common form of defective inactivation of mutant Na channels is associated with what 3 things? What causes thi defect>

Answer 17

A common form fo defective inactiavtion exhibited b mutant Na channels is associated with hyperkalemic periodic paralysis, long QT sundrome and inherited epilepsu. The defect is caised by incomplete closure of the inactivation gate resulting in an increased level of persistent current as compared with Na channels with normal inactivation

Question 18

What current is the cardiac pacemaker current

Answer 18

If funny channel

current is carried by yeperpolarixation-activated cyclic nucletotide gated channels also known as HCN channels. it is a depolarizing current carried mainly by Na ions (although HCN channels are also permeable to K ions) It is gated by voltage and regulated by cAMP. Binding of cAMP facilitates HCN channel activation. There are four members in the HCN family of channels (HCN1-HCN4). The predominant form expressed in cardiac SAN cells is HCN4

Question 19

what regulates HCN channels?

Answer 19

cAMP biding induces a positive shift in the activation of HCN channel. it also accelerated HCN channel activation

Question 20

Why does the electrical signla go in one direction?

Answer 20

Na inactivation (refractory period!) during plateau phase of AP Na channel is inactivated bc the cardiac cell is in the depolarized state and a depolarized cell is not excitable during its refractory period

Repolarization of membrane, displacement of channel-inactivating segment, and closure of gate is slow (several ms)

recovery from inactivation is time and voltage dependent (repolarization potential more neg that -60mV))

Question 21

WHat are the 3 types of refractory periods? What causes the refractory period in nodal cells?

Answer 21

Absolute refractory period: period during an action potential when another AP cannot be generated due to inactivated NA channels

Relative Refractory Period: period during repolarization when a strong stimulus can generate an action potential

Effective Refractory Period: poeriod that extends a little beyond Absolute refractory period where depolarization can occur but not enough to generate AP

**In nodal cells the refractory period is due to the inactivation of CA channels, the effective refractory period extends beyond the end of the action potential. this is due to the longer time it takes for the CA channels to recover from inactiation (Ca mediated no Na)