M2-C5-L16 --> Electrical Conduction Of Heart

Front 1

SKELETAL MUSCLE ACTION POTENTIAL

- resting potential?

- peak potential upon depolarization?

- duration of 1 AP?

Back 1

-85 mV

+30 mV

2.5 ms

Front 2

SKELETAL MUSCLE ACTION POTENTIAL

- describe the graphic description of a single AP

Back 2

- resting potential @ -85 mV
- rapid upstroke
- peak potential @ +30 mV
- rapid downstroke back to resting potential
- duration is 2.5 ms

Front 3

AP graph of Cardiac Muscle

Back 3

Front 4

CARDIAC MUSCLE ACTION POTENTIAL

- resting potential?
- phase # at the resting potential?

- how many phases total?
- depolarization peaks @ what mV?
- duration of 1 AP?

Back 4

-90 mV to -85mV

- Phase 4 @ resting potential

- Total of 5 phases (4, 0, 1, 2, 3)
- (+20mV)
- 400 ms

Front 5

SKELETAL AP vs. CARDIAC AP

- major differences? x3

Back 5

- Skeletal is Biphasic
- Skeletal lacks phase 1 & 2
- Skeletal has very short duration

Front 6

CARDIAC AP

- Transmembrane potential exists due to?

Back 6

- Separation of Positive & Negative charges @ the membrane

Front 7

CARDIAC AP

Describe:
- Phase 0
- Phase 1
- Phase 2
- Phase 3
- Phase 4

Back 7

- Upstroke

- Partial Repolarization (Overshoot)
- Plateau

- Repolarization
- Resting Potential

Front 8

TEMPORAL RELATIONSHIP BTW
TENSION DEVELOPMENT
&
MEMBRANE POTENTIAL CHANGE

- what PREcedes contraction?

Back 8

- Rapid Depolarization

Front 9

TEMPORAL RELATIONSHIP BTW
TENSION DEVELOPMENT
&
MEMBRANE POTENTIAL CHANGE

- completion of repolarization coincides with?

Back 9

- Peak Tension Development

Front 10

TEMPORAL RELATIONSHIP BTW
TENSION DEVELOPMENT
&
MEMBRANE POTENTIAL CHANGE

- Duration of AP parallels what?

Back 10

- Duration of contraction

Front 11

TEMPORAL RELATIONSHIP BTW
TENSION DEVELOPMENT
&
MEMBRANE POTENTIAL CHANGE

- reason for difference btw muscle twitch & AP is due to?

Back 11

- Excitation-Contraction Coupling

Front 12

Temporal Relationship BTW
Tension Development
&
Changes in Membrane Potential

Back 12

UP ARROW
- Rapid Depolarization PRECEDES the Peak of Contraction

DOWN ARROW
- Completion of Repolarization COINCIDES with Peak Tension Development

HORIZONTAL ARROWS
- Duration of contraction PARALLELS the Duration of AP

Front 13

CARDIAC AP

- what are the 2 type of Cardiac AP's?

Back 13

- Fast Response

- Slow Response

Front 14

CARDIAC AP

- Fast response AP involves what anatomical structures? x3

Back 14

- Atrial Myocytes
- Ventricular Myocytes
- Purkinje Fibers

Front 15

CARDIAC AP

- Slow response AP involves what anatomical structures? x2

Back 15

- SA node

- AV node

Front 16

CARDIAC AP

- major differences btw Fast response AP vs. Slow response AP

Back 16

(UREA)

During Fast Response
- Upstroke Slope is greater
- Resting Vm more negative
- Extent of Overshoot greater
- Amplitude of AP greater

Front 17

CARDIAC AP

- what variable changes accounts for the various phases of Cardiac AP?

- how does the above have any effect?

Back 17

- Changes in PERMEABILITY of cell membrane

- Alters rate of ion passage across membrane

Front 18

CARDIAC AP

- when accounting for the various changes of cardiac AP, the cell membrane permeability involves the altering the rate of passage for what ions mainly? x3

Back 18

- Na+

- Ca2+

- K+

Front 19

CARDIAC AP

- define Permeability

Back 19

Net Quantity of Ion
that will Diffuse across
each
Unit Area of membrane
per
Unit Concentration Difference
across the membrane
per
Unit Time

Front 20

CARDIAC AP

- define Equilibrium Potential

Back 20

Electrical Potential required
to
Counterbalance
Concentration Gradient
so
NO Net Ion Movement occurs

Front 21

CARDIAC AP

Equilibrium Potenital for:
- Na+
- Ca2+
- K+

Back 21

70 mV

- 94 mV

- 132 mV

Front 22

CARDIAC MUSCLES
Ion Concentration & Equilibrium Potential

Back 22

Front 23

what does the -94 mV mean?

Back 23

EQUILIBRIUM POTENTIAL
is
the charge (potential) needed
to
Keep All the K+ ions Inside the Cell

(to counterbalance the Concentration Gradient)

Front 24

RESTING POTENTIAL: IONIC BASIS

- what are the 2 OPPOSING FORCES involved in moving ions, such as K+?

Back 24

- Chemical

- Electrostatic

Front 25

RESTING POTENTIAL: IONIC BASIS

- Cell Membrane is relatively permeable to what ion?

Back 25

K+

(Pk+ >> Pna+ , Pca++)

Front 26

RESTING POTENTIAL: IONIC BASIS

[K+]in >> [K+]out : this favors what?

Back 26

- Outward Diffusion

Front 27

RESTING POTENTIAL: IONIC BASIS

- as K+ diffuses out, what is retained within cell?

- with respect to outside, K+ diffusion leaves the cell interior in what state?

Back 27

- Anions retained withiin cell

- Electronegative interior
(w/ respect to outside)

Front 28

RESTING POTENTIAL: IONIC BASIS

- at equilibrium, what is equal?

Back 28

Chemical forces = Electrostatic forces

Front 29

RESTING POTENTIAL & K+

- what is Ek?
(aka?)

- how is above value obtained?

Back 29

- Electrostatic Force of Potassium
(Nernst potential for K+)

- Nernst Equation

Front 30

RESTING POTENTIAL & K+

- Nernst Potential for K+ = Ek = ???
- Ek is oriented how?
- Ek is required for?

Back 30

-90mV to -100mV

Oriented with INSIDE cell being more NEG. than outside

Counterbalance the Chemical Potential for K+

Front 31

RESTING POTENTIAL & K+

- Membrane Potential (Vm) at rest?

- IF the K+ were the ONLY Permeant ion, then?

Back 31

-80mV to -90mV

Ek = Resting Vm

Front 32

RESTING POTENTIAL & K+

- which is more negative: Ek or Vm?

Back 32

Ek is more negative than Vm

Front 33

RESTING POTENTIAL & K+

- since Ek (-90mV to -100mV) is more negative than Vm (-80mV to -90mV), what is the result?

Back 33

Small Potential (10 to 15mV) tends to Drive K+ out of cell

Front 34

NA+ EQUILIBRIUM POTENTIAL

- what is the Ena?

- above Electrostatic force is oriented how?

- above Ena is required to do what?

Back 34

40mV to 70mV

Oriented with INSIDE of cell more POSITIVE than outside

Required to counterbalance the Chemical Potential for Na+

Front 35

NA+ EQUILIBRIUM POTENTIAL

- is Na+ concentration greater outside or inside?

- what is the Vm?

Back 35

outside

-80 mV to -90mV

Front 36

NA+ EQUILIBRIUM POTENTIAL

Since [Na+]out >> [Na+]in,
AND
Ena = 40mV to 70mV
AND
the Vm is -80mV to -90mV,
what is the result?

Back 36

There is a Large
Electrical & Chemical gradient
tending to
PULL
Na+
INTO the Cell

Front 37

NA+ EQUILIBRIUM POTENTIAL

- is the permeability of Na+ high or low?

- what is the consequence?

Back 37

- Low Na+ Permeability

- Na+ entry into cell is also very low

Front 38

NA+ EQUILIBRIUM POTENTIAL

Since Na+ has a large chemical & electrostatic gradient driving Na+ inside,
BUT
has a low permeability allowing low entry into cell,
what is the result?

Back 38

Small inward CURRENT of Na+

Front 39

NA+ EQUILIBRIUM POTENTIAL

- small inward current causes what?

Back 39

causes
Vm
to be slightly LESS NEGATIVE
than
predicted value of Nernst Eq.
for
POTASSIUM (K+)

Front 40

NA+ EQUILIBRIUM POTENTIAL

- External Na+ concentration has very little effect on what?

- External Na+ concentration has a very large effect on what?

Back 40

- Vm

- Active Membrane
(Depolarizing Cell)

Front 41

GOLDMAN EQUATION

- Goldman Eq. explains what?

- Thus, the Goldman Eq. will imply what?

Back 41

- how Permeability of More than One ION influences Membrane Potential

- RELATIVE (not absolute) Permeabilities determine Vm

Front 42

GOLDMAN EQUATION

- at rest compare the permeabilities of K+ and Na+

Back 42

Pk is 100 times more than Pna

Front 43

ACTIVE TRANSPORT'S ROLE

T/F: the Cell is in Equilibrium for K+ and Na+

Back 43

False

(K+ and Na+ is NOT in equilibrium)

Front 44

ACTIVE TRANSPORT'S ROLE

- the active transport will counter what? x2

- what is the important active transport called?

Back 44

- Loss of K+
&
- Gain of Na+

- Na+/K+ ATPase

Front 45

ACTIVE TRANSPORT'S ROLE

- Na+/K+ ATPase requires what?

- for what?

Back 45

- Energy required

- to Move Na+ against EC gradient

Front 46

ACTIVE TRANSPORT'S ROLE

- Na+/K+ ATPase does what? x2

- what is the effect of above?

Back 46

Pumps 3 Na+ OUT
&
Pumps 2 K+ IN

Makes cell INSIDE more NEGATIVE
(b/c Eq. Potential for Na+ = +70mV & K+ = -94mV)

Front 47

ACTIVE TRANSPORT'S ROLE

- Na+/K+ ATPase effects on membrane?

- via what process?

Back 47

- Depolarizes membrane

- Partial Pump Inhibition

(depolarize membrane by dissipating the EC gradient)

Front 48

ACTIVE TRANSPORT'S ROLE

- Na+/K+ ATPase activity is increased how? x2

Back 48

- Increase in Na+ INSIDE
OR
- Increase in K+ OUTSIDE

Front 49

FAST RESPONSE: IONIC BASIS

- Threshold needed for?

- what is the Threshold for Cardiac Fast Response?

Back 49

Potential needed to generate AP

-75 mV

Front 50

FAST RESPONSE: IONIC BASIS

Threshold Potential is the Potential at which ______ generated by _______ are sufficient enough to initiate __________ in which subsequent _______ becomes _____________ of the _________.

Back 50

- Inward Currents

- Membrane Depolarization

- REGENERATIVE AP's

- Depolarization

- INDEPEDENT

- of the Initial Stimulus

Front 51

PHASE 0 : UPSTROKE

- what does gNa mean?

Back 51

- Sodium Conductance

(thru fast sodium v-gated channels)

Front 52

PHASE 0 : UPSTROKE

- Upstroke is due to what? thru what?

Back 52

Sudden Increase
in
Sodium Conductance
thru
Fast Sodium Channels

Front 53

PHASE 0 : UPSTROKE

- Fast Sodium Channels are what kind of mediated channels?

Back 53

- Voltage Gated channels

Front 54

PHASE 0 : UPSTROKE

- as gNa suddenly increases, what happens to gK?

- gCa?

Back 54

- Suddenly drops, plateaus, then returns to baseline

- Slowly goes up, than drops to baseline even slower.

Front 55

PHASE 0 : UPSTROKE

- thus the ionic etiology of the Phase 0 rapid upstroke is?

Back 55

- rapid increase in gNa

Front 56

SODIUM (Na+) MOVEMENT @ PHASE 0

- Channels involved?

- Na+ Activation gate called?

- Na+ Inactivation gate called?

Back 56

- Fast Sodium Channels (V-gated)

- m gate

- h gate

Front 57

SODIUM (Na+) MOVEMENT @ PHASE 0

CELL @ REST
Resting cell Vm?

[Na+]out =?

[Na+]in = ?

Ena = ?
(what kind of force is this?)
(what does this force favor?)

Back 57

-90 mV

145 mM

10 mM

60 mV
(Chemical Force)
(Favors Na+ Inward Flux)

Front 58

SODIUM (Na+) MOVEMENT @ PHASE 0

CELL @ REST
- since the Vm = -90mV, what can be said about the Electrical Force?

Back 58

90 mV of Electrical Force favors INWARD Na+ Flux

Front 59

SODIUM (Na+) MOVEMENT @ PHASE 0

CELL @ REST
- Chemical Force? Favoring?
- Electrical Force? Favoring?

- Total EC Force? Favoring

Back 59

Chemical Force = Ena = 60 mV
(favoring Na+ INFLUX)

Electrical Force = -90 mV
(favoring Na+ INFLUX)

Total EC Force = 60 - (-90) = 150 mV
(favoring Na+ INFLUX)

Front 60

SODIUM (Na+) MOVEMENT @ PHASE 0

CELL @ REST
- Despite the Total EC Force for Na+ being really high (150 mV), why would there by virtually no Na+ movement across the resting cell membrane?

Back 60

- Closure of m gates

thus the gNa is very low

Front 61

SODIUM (Na+) MOVEMENT @ PHASE 0

CELL @ REST
- Closure of which gate implies a very low gNa+?

Back 61

- Closure of m gates.

Front 62

SODIUM (Na+) MOVEMENT @ PHASE 0

- when would you have activation (opening) of m gates?

Back 62

when membrane depolarizes to -65 mV

Front 63

SODIUM (Na+) MOVEMENT @ PHASE 0

- Activation (opening) of m gates is ___ dependent.

- M gate opening is _______ process

Back 63

- Voltage Dependent

- Regenerative Process

Front 64

SODIUM (Na+) MOVEMENT @ PHASE 0

- as m gates open, Na+ enters the cell and does what to the charges inside?

- this causes what effect on Vm

Back 64

- Neutralizes negative charges

- Reduces Vm

Front 65

SODIUM (Na+) MOVEMENT @ PHASE 0

- as m gates open, the influx of Na+ will reduce the Vm initiating what? x2

Back 65

- Further opening of m gates

leading to

- Further reduction in Vm

Front 66

SODIUM (Na+) MOVEMENT @ PHASE 0

- as m gates open, and Na+ enters cells what is the effect on the gradients?

Back 66

- Electrical gradient REDUCED as Na+ moves into cell

- Concentration gradient is not affected much

Front 67

SODIUM (Na+) MOVEMENT @ PHASE 0

T/F : the concentration gradient of K+ is appreciably affected by the inward flux of Na+ when m gates open.

Back 67

False

(both concentration gradients of Na+ and K+ is not affected appreciably)

Front 68

SODIUM (Na+) MOVEMENT @ PHASE 0

- with Na+ influx (via m gate openings), the Vm approaches 0, causing the Electrical gradient to have what influence on Na+ influx?

Back 68

- Electrical gradient exerts PROGRESSIVELY less influence on Na+ influx

(as Vm approaches 0)

Front 69

SODIUM (Na+) MOVEMENT @ PHASE 0

- with m gates open, Na+ enters cell via what gradient primarily?

Back 69

- Concentration gradient

Front 70

SODIUM (Na+) MOVEMENT @ PHASE 0

- the continued influx of Na+, as Vm approaches 0, leads to what event?

Back 70

- POSITIVE Overshoot

Front 71

SODIUM (Na+) MOVEMENT @ PHASE 0

- what terminates the Na+ influx?

Back 71

- Closure of h gates

Front 72

SODIUM (Na+) MOVEMENT @ PHASE 0

- h gates are ______ dependent

Back 72

- voltage dependent

(just like m gates, dependent on membrane potential)

Front 73

SODIUM (Na+) MOVEMENT @ PHASE 0

- m gates open at what general rate?

- h gates open at what general rate?

Back 73

- rapidly (0.1 to 0.2 ms)

- slowly (>1 ms)

Front 74

SODIUM (Na+) MOVEMENT @ PHASE 0

- H gates remain closed until?

- above occurs in what phase?

Back 74

- cell has partially repolarized

- phase 3

Front 75

SODIUM (Na+) MOVEMENT @ PHASE 0

- Until the H gates partially open, the cell remains in?

- By the above mechanism, what is prevented?

Back 75

- Refractory mode to further excitation

- Sustained, Tetanic Contractions of Heart are prevented

Front 76

SODIUM (Na+) MOVEMENT @ PHASE 0

- Even after the Electrical gradient is dissipated, the Chemical gradient drives what?

- until?

- what cellular condition closes the h gates?

Back 76

- Na+ INFLUX

- Net ElectroNeutrality

- ElectroPositivity
(Vm = +30 mV)

Front 77

SODIUM (Na+) MOVEMENT @ PHASE 0

- what event completes Phase 0?

Back 77

- h gate closure

Front 78

PHASE I : EARLY REPOLARIZATION

- Phase I reflects what initial influence?

Back 78

- Inactivation of Fast Sodium Channels

Front 79

PHASE 2 : PLATEAU

- Phase 2 is mainly due to?

- Phase 2 is also due to?

Back 79

- Influx of Ca2+

- also Na+ influx

Front 80

PHASE 2 : PLATEAU

- Ca2+ & Na+ influx is achieved via what type of channels?

Back 80

- Slow channels

Front 81

PHASE 2 : PLATEAU

- what currents are created by Ca2+ and Na+?

Back 81

- Slow, Inward Ca2+ & Na+ currents

Front 82

PHASE 2 : PLATEAU

- Slow, inward Ca2+ and Na+ currents are balanced by?

- thus producing what?

Back 82

- Small, OUTWARD K+ current

- Maintaining Prolonged Plateau

Front 83

PHASE 2 : PLATEAU

- the balancing of Ca2+ & Na+ small inward currents, with a small outward current of K+, will maintain a prolonged plateau @ what Vm?

Back 83

- Vm close to 0

Front 84

PHASE 2 : PLATEAU

- slow channels open at what threshold?

- once slow channels open, describe the movement of ions.

- what gradient is involved above

Back 84

- 30 to -40 mV

Ca2+ and Na+ begin to move into cell

via
Electro-Chemical gradients
(but Chemical gradient is primary)

Front 85

PHASE 2 : PLATEAU

- After Phase 1 early repolarization, Vm is roughly 0, so ______ gradient for Ca2+ & Na+ provide ______ for ______ via ______

Back 85

- Chemical

- Primary Force

- Ca2+ & Na+ INFLUX
via
-Slow channels

Front 86

PHASE 2 : PLATEAU

- what ion and channel is involved in Excitation-Contraction Coupling?

Back 86

- Ca2+ that enter via Slow Channels

Front 87

CALCIUM INDUCED CALCIUM RELEASE

- Excitation-Contraction coupling implies what?

- what is DHP?

- DHP function?

- where do you find DHP's?

Back 87

- by the time you complete AP, you have greatest contraction

- Voltage Gated Calcium Channel

- allows for Ca2+ influx

- surface of Cardiomyocytes

Front 88

CALCIUM INDUCED CALCIUM RELEASE

- what is RYR?

- where would you find RYR's?

- Ca2+ binding to RYR does what?

Back 88

- Ligand-gated Ca2+ channels

- Sarcoplasmic Reticulum

- Release large amount of Ca2+ from SR stores.

Front 89

CALCIUM INDUCED CALCIUM RELEASE

- what does it mean for Ca++ induced Ca++ release?

Back 89

- Ca2+ influx via DHP will enter cell and bind to RYR, thus triggering a large release of Ca2+ from SR stores

Front 90

CALCIUM INDUCED CALCIUM RELEASE

- why is the usage of RYR so important in contraction?

Back 90

- 90% of Ca2+ needed for cardiomyocyte contraction come from SR stores.

Front 91

ISOLATED EFFECTS:
GUINEA PIG PAPILLARY MUSCLE

- experiment showed factors influencing what?

Back 91

- Factors influencing SLOW, INWARD Current

Front 92

ISOLATED EFFECTS:
GUINEA PIG PAPILLARY MUSCLE

- what are the factors/drugs that influenced the Slow, Inward, Current? x2

Back 92

- Catecholamines

- Calcium Channel Blockers

Front 93

ISOLATED EFFECTS:
GUINEA PIG PAPILLARY MUSCLE

- Catecholamines do what effect? x2

- List 2 examples of Catecholamines that do this?

Back 93

- Increase Slow Inward Ca2+ current

- Increase Contractability

- Epinephrine
- NE

Front 94

ISOLATED EFFECTS:
GUINEA PIG PAPILLARY MUSCLE

- Calcium Channel Blockers do what effects? x2

- List 3 examples of Calcium Channel Blockers

Back 94

- Decrease the Slow, Inward Ca2+ current

- Decrease Contractability

(DNV)
- Diltiazem
- Nifedipine
- Verpamil

Front 95

CALCIUM CHANNEL BLOCKERS

- application of Diltiazem will have what effect on AP?

- Force of Contractility?

Back 95

- Decrease AP

- Decrease Force

Front 96

CALCIUM CHANNEL BLOCKERS

- increasing the dosage of Diltiazem will effect AP and Force of Contractility how?

Back 96

- will Progressively DECREASE both.

Front 97

ANOMOLOUS RECTIFICATION

- in NERVE cells, increased gK contributes to?

- in HEART cells, what happens with gK?

Back 97

- Rapid Repolarization

- gK decreases after initiation of propagated AP

Front 98

ANOMOLOUS RECTIFICATION

- in the Heart, the decrease in gK after AP will have what effect on K+ rate?

- this causes what?

Back 98

- Reduces rate at which K+ leaves the cell

- Prevents Repolarization of Cell during Plateau phase

Front 99

ANOMOLOUS RECTIFICATION

- what balances the Slow, Inward currents of Ca2+ and Na+?

- this balance allows for?

Back 99

- Outward, Slow K+ current

- Maintenance of the prolonged plateau
(seen in phase 2)

Front 100

PHASE 3 : REPOLARIZATION

- Phase 3 depends on what 2 processes?

Back 100

- Increased gK

- Inactivation of Slow, Inward Ca2+ & Na+ currents

Front 101

PHASE 3 : REPOLARIZATION

- in phase 3, gK is increased or decreased?

- characterize the gK in Phase 3. x2

Back 101

- Increased gK

- Voltage Dependent
- Self-Regenerative