Cardiac membrane potential

Question 1

What is the order of activation of the heart?

Answer 1

SA node (pacemaker)
R & L atria
AV node (slows down)
His purkinje (super fast)- synchronize
-bundle of his
-bundle branches
-purk cells: endo to epi

Question 2

What is the function of the sodium-potassium pump?

Answer 2

takes 3 Na out
brings 2 K in
maintains the gradient

Question 3

What is the function of the Na-Ca exchanger?

Answer 3

tries to keep calcium concentration low inside the cell
takes 1 ca out
brings 3 Na in
*driven by the sodium gradient set up by the pump

Question 4

What is the normal concentr of extracellular potassium?

Answer 4

between 3 to 5 mM

Question 5

What is anomalous rectification?

Answer 5

• Nerst equation predicts that at lower extracell [k] the K+ should be leaving the cell but it doesn’t
• there’s a decrease of K+ permeability whenever there is an increased driving force on K
  e. g. hypokalemia or depol of membr

*via IK1 channel

Question 6

What happens in hypokalemia?

Answer 6

extracell [K] is less than 3mM
incr gradient for K to leave the cell
doesn’t due to decr permeability (anomalous rectification)
result: no change in RMP

Question 7

What happens in hyperkalamia?

Answer 7

extracell [K] is more than 5mM
causes membrane to be more permeable
but K stays inside -> more + RMP
-now got less Na channels available: fast AP upstroke decr and conduction slows

Question 8

What happens in an MI?

Answer 8

RMP depolarizes (+) so Na channels are less available
no AP
infarcted regions can have K+ leaking out, local hyperkalemia
-slows conduction -> can lead to re-entry

Question 9

How do potassium channels delay repolarization?

Answer 9

cuz rectification
when voltages are more positive than the K equilibrium (e.g. action potential plateau)
much outward K flow is not allowed

in other words, during the AP plateau K+ permeability decreases, delaying repolarization

Question 10

What are fast responses?

Answer 10

Na channels!

have fast rate of rise and high amplitude

Question 11

What are slow responses?

Answer 11

L type Ca channels!
have slow rate of rise and lower amplitude
*have short space constant cuz less gap junctions
plus have higher resistance cuz smaller cells

Question 12

Describe the phases of the cardiac AP

Answer 12

Phase 0: upstroke- activation of fast sodium channels (membr potential approaches E-Na (+) [net inward]
Phase 1: Na channels close, K channel (I-TO) transiently open [net outward]
Phase 2: plateau phase- L type Ca channels open
background IK1 channel decrease (inward rectification) [net inward]
Phase 3: Ca channels close and iK1 conductance increases (reversal inward rectification) [decr outward]
Phase 4: repolarization- background K conductance (iK1) high, delayed iK channels deactivated
Ca channels closed and Na channels recover but remain closed [back to rest]

Question 13

What is the effect of tetrodotoxin on purkinje fiber AP?

Answer 13

block fast Na channels (Phase 0)
slow Ca channels not affected so they carry phase 0
rest of phases unchanged
net result: slow response AP

Question 14

Slow vs Fast response

Answer 14

Slow: SA & AV node
phases: 0, 3, 4
low membr potential, low threshold, slow upstroke, short duration, slow conduction!

Fast: atrial, His-Purk, ventricular
Phases: all
high membr potential, high threshold, fast upstroke, long duration, fast condition!

Question 15

What are the characteristics of SA/AV node cells?

Answer 15

small! short space constant, few gap jnct = slow conduction
few myofibrils = weak contraction

function: pacemaker

Question 16

What are characteristics of atrial and ventricular muscle?

Answer 16

medium! lotz of gap junct = rapid conduction
lotz myofibrils = strong contraction

function: conduction/contraction

Question 17

What are characteristics of His-Purk cells?

Answer 17

large cells! lotzz gap junct = rapid conduction
few myofibrils = weak contraction

function: very rapid conduction

Question 18

What is an intercalated disc?

Answer 18

Specialized region of intercellular connections b/w cardiac cells

• types of adhering junctions
  1. fascia adherens: anchor site for actin
  2. macula adherens (desmosomes): hold cells together during contraction by binding interm filaments
  3. gap junctions: low resistance connections that allow current (AP) to conduct
• primary determinant of internal resistance in cardiac tissue
• senstive to intracell [Ca] and [H+]

Question 19

What is healing over?

Answer 19

increase in internal resistance due to decrease of open gap junctions
caused by increase of intracell [Ca] and [H+] after an MI
*electrical isolation fo damaged tissue

Question 20

What are the factors that determine cardiac function?

Answer 20

1. space constant!! (Rm/Ri)^1/2
   Rm is inversely related to K+ permeability (low K causes decr K permeability which increases membr resistance)
   Ri is inversely related to # of gap junctions & inv related to diameter
2. rate of rise and amplitude of AP
   - lvl of resting membr potential (for fast responses) [rem the more positive, the less Na channels available]
   - slow vs fast AP
   - premature responses initiated during RRP

Question 21

What conditions influence the AP upstroke?

Answer 21

those that change RMP (more + = inactivated Na channels)
e.g. hyperkalemia: make it more +
premature excitation during RRP- slower upstroke
ischemia/MI: damaged cells release K+ so depolarize RMP

Question 22

What conductions can you see on an EKG?

Answer 22

P-R interval: conduction from atria to ventricles

QRS: conduction through ventricles

Question 23

What can you tell me about AV node conduction?

Answer 23

delays conduction to allow ventricular filling
AP is slow response cuz slow inward Ca current
long refractory period (can’t get another AP)
-Protects ventricles from abnormally high atrial rates

*determined by P-R interval

Question 24

What are examples of AV nodal conduction abnormalities

Answer 24

heart block!
1st degree: abnormal prolongation of PR (greater than 0.2s)
2nd degree: some atrial impulses fail to activate ventricles
-not all p waves followed by qrs (diff ratios)
Mobitz type I: progressive lengthening of PR then shortening, drop beats
Mobitz type II: same PR but still drop beats
3rd degree: complete AV nodal block
-no consistent PR interval

atrial flutter or fibrillation: when atrial rhythm is going way too fast
-thankfully long refractory period protect the ventricles

Question 25

What can you tell me about ventricular conduction?

Answer 25

rapid conduction through His-Purk!
endo to epi
narrow QRS (less than 100msec)
synchronized
QRS interval!

Question 26

What are some examples of abnormal ventricular conduction?

Answer 26

-slurred QRS= slowed intraventricular conduction. abnormal wall motion
causes? hyperkalemia, ischemia, ventricular tachy
-notched QRS= asynchronous activation of LV & RV
causes? L and/or R bundle branch blocks
-ventricular conduction through diff types of tachycardia
e.g. supraventricular tachycardia (SVT): conduction has normal pattern but just fast. coming from atria, normal wall motion, QRS duration normal, SV not sig compromised
e.g. ventricular tachycardia (VT): impulse originates from ventricular muscle- slower plus abnormal conduction pattern = abnormal wall motion, SV compromised
-slurred QRS

Question 27

What can you tell me about atrial conduction? plus abnormalities

Answer 27

represented by p wave
atrial fibrillation: no discreet p wave
-not fatal cuz only contribute 5%
it can become ventricular fibrillation (conduction abnormality)
-asynchronous, cardiac output drops -> fatal
*both due to re-entry of excitation

Question 28

What is the effect of parasympathetic innervation to the heart?

Answer 28

through Ach on muscarinic receptors

• incr K+ permeability: hyperpolarize membr
• inhibit adenylate cyclase activity + cAMP synth: dear slow inward Ca
• inhibit atrial muscle contraction: negative ionotropic effect
• inhibit SA node: slow HR, lengthen R-R
• inhibit AV node: lengthen P-R interval

Question 29

What is the effect of sympathetics innervation to the heart?

Answer 29

affects all areas!
via beta 1 -> incr cAMP
-incr slow inward Ca current
-incr atrial/ventri muscle contraction: + ionotropic effect
-incr SA node rate: incr HR, decr R-R
-incr AV node conduction: decr P-R