Cardiac Electrophysiology I Flashcards

1
Q

resting cardiac muscle cell

A
  • biophysicists look at the cell from the inside

- electrocardiologists look at the cell from the outside

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

types of biological electrical potentials

A
  • equilibrium potential
  • gibbs donnan equilibrium
  • diffusion potential
  • epithelial membrane potentials
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

equilibrium potential

A
  • voltage obtained for a given concentration gradient of a single ion at equilibrium across a semi permeable membrane
  • given single ion and represent by nernst equilibrium equation
  • Na is 60
  • K is -90
  • Ca is 120
  • if membrane is more permeable to one of the ions, the resting potential is closer to it
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Gibbs-Donnan equilibrium

A
  • special
  • impermeable polyelectrolyte on one side of a membrane that is permeable to salts
  • capillary membranes if albumin and other charged plasma proteins are in the blood but not the interstitial fluid
  • pH different from isoelectric point of the polyelectrolyte, leads to unequal distribution of salts across the membrane and slight potential that has the same sign as the charge on the polyelectrolyte
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

diffusion potential

A
  • when two or more ions are permeable to a membrane, but the various ions have different permeabilities
  • calculated by goldman hodgkin katz equation using the theory of electrodiffusion
  • independent passive movements of ions across membranes under influence of their concentration gradients and electrical forces
  • cell resting potential and action potentials are diffusion potentials
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

epithelial membrane potentials

A

-differences in electric potential between two dilute solutions when the membrane itself it a layer of cells
kidney and GI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

nernst equilibrium for K

A
  • raising external K decreases outward K gradient and makes Ek less negative, which is depolarizing
  • raising internal K increases outward flow of K and makes Ek more negative, hyperpolarizing
  • at low external K, membrane potential is more positive than predicted by nernst equation due to Na presence inside the cell that brings the charge difference back down (more positive)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

raising internal K

A

increases the gradient out and makes Em more negative inside- hyperpolarizing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

raising external K

A

decreases the gradient out and makes Em more positive inside- depolarizing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

raising internal Na

A

-decreases gradient in and makes the membrane more negative- hyperpolarizing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

raising external Na

A

-increases gradient in and makes the membrane more positive- depolarizing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

GHK diffusion potential

A
  • equation includes permeabilities of whatever ions happen to be moving- a is Pna/Pk
  • chloride is in equilibrium and doesn’t have any pumps, which is why its not in the equation
  • accounts for biological diversity of cell membrane diffusion potentials
  • different cells have different permeability constants and therefore different membrane potentials (compared to nernst prediction of all the same since concentrations of K are the same)
  • nerve and muscle cells much more permeable to K, Em -80, alpa is 0.05
  • RBCs a is 1/4, so resting potential only -11mV
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

conductance

A
  • predicted by current voltage plot
  • outward currents of pos ions are pos, inward are neg
  • conductance is 1/R
  • depends on number of open channels
  • Ohm’s law predicts linear
  • biological channels not Ohmic-rectification, conductance differs for inward and outward currents
  • iK=Gk (Em-Ek)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

outward rectification

A
  • conductance of outward currents is greater than for inward
  • current voltage slopes up non-linearly
  • closed at hyperpol, open at depol (when membrane potential is positive)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

inward rectification

A
  • conductance of inward currents is greater than for outward currents
  • current voltage plots slope downward non-linearly
  • closed at depol, open at hyperpol (when membrane potential is negative)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

K+ channel

A
  • iK1
  • resting potential
  • inward rectifier
  • cell is hyperpolarized at rest, conductance of the channel is high
  • upon depolarization, the conductance is less, allowing inward Na to depolarize membrane potential
  • upon repolarization, iK1 re acquires high conductance, maintaining inside neg resting potential
  • direction of current flow depends on electrical and ionic concentration gradients
  • inward rectifier iK1 mediates a positive efflux of K (brings K in which increases gradient and causes more to leak out)??
17
Q

molecular structure of mammalian potassium channel

A
  • 4 identical subunits
  • transmembrane domain forms a pore that allows the ions to cross the membrane
  • the selectivity filter filters out the ions other than potassium
  • ion selectivity depends on the strength of the electric filed at the binding site and on the size of the hydrated ion
18
Q

single file electro diffusion

A

-three K ions may simultaneously occupy a channel but do not pass each other in transit

19
Q

channel blockers

A
  • occlude calcium at extracellular side
  • can reduce heart rate and contractility
  • lower CO and BP
  • ACE inhibitors block conversion of angiotensin I and II relax smooth muscle decreasing TPR and BP
20
Q

membrane voltage and open channels

A
  • cell becomes more permeable to a certain ion
  • the Vm moves closer to the Ex of that ion
  • when a cardiac muscle cell at -60 becomes permeable to Na, INa increases and Na flows in and the value of Vm moves toward 60, causing the depolarizing upstroke of the AP
  • concentration doesn’t change much
21
Q

three stage model for Na and Ca channels

A
  • open, inactivated, closed
  • charged domain is voltage sensor that responds to membrane voltage and causes conformational change in channel that opens outwardly rectifying channels-conductance low at hyperpolarization
  • open at a threshold and cause more depol
  • even if voltage inside is pos, concentration gradient still drives movement
  • membrane switches from neg to pos, moves from Ek to Ena
  • sodium channels rapidly inactivate- h gates, occludes cytoplasmic side
  • inactivation in Ca much slower
  • both progress to closed with m gate down and h gate up
22
Q

refractory periods

A
  • comes from inactivation
  • absolute-no AP-inactivation gates mostly closed, inward current can’t reach another threshold
  • relative-normal stim not good enough, but raising stim does give AP; some but not all channels have returned to resting state
  • refractory period in cardiac is diastole- heart can refill with blood
  • prevents chambers from contracting before they have enough blood
23
Q

lower membrane potential

A
  • reduces rate of depol and amp of AP
  • initial resting potential more depolarized than usual, some channels inactivated, AP is smaller and slowing
  • ischemia will depolarize resting potential
24
Q

stimulating voltage

A
  • if stimulating voltage to threshold has slower upstroke (takes longer to reach threshold)
  • some channels will inactivate before they get the chance to do anything
  • AP smaller and slower upstroke
  • AV node- arrhythmias from small AP with slow uptakes
25
Q

voltage gated activation of outwardly rectifying K channels

A
  • charged transmembrane domains move when the transmembrane voltage becomes pos (depol)
  • lever causes a change in the conformation of the channel pore, thereby opening channel
  • conductance is higher at depolarized than at hyperpolarized voltages and currents are outward for K channel
  • works toward repolarizing
  • not leak channels
26
Q

evolution

A

gave us many different types of channels
calcium and sodium probably related
-potassium and camp related

27
Q

delayed rectifying K channels

A
  • activate with time delay and inactivates by ball and chain mechanism
  • repolarization by bringing K out
  • open at depol with delay
28
Q

cardiac action potentials in different regions

A
  • SA and AV from Ca out and K in
  • all others are variations with Na in, Ca in delayed and K out
  • a lot slower than muscle cell AP and there is no plateau in skeletal muscle
29
Q

purkinje fiber AP

A
  • resting potential is -90
  • overshoot is 30
  • amp up to 120 mv
  • low internal resistance
  • long duration with long refractory period-prevents ventricular muscle from reactivating the conducting system
  • membrane conductance is high early in the plateau, but falls at the end of the plateau
  • this is because Ca in and K out are almost balanced, both currents decline and then the delayed rectifier channels open and repolarize the membrane
  • see last slide- very important