Lecture 6: Cardiac Muscle, Excitation and Signaling

Question 1

What are the fundamental characteristics of the heart beat?

Answer 1

1. heart beat is myogenic, but can be influenced by nervous and hormonal factors
2. myocardial contraction is all-or-none (every cell beats together)
3. Atria contract first, and after a small delay, the ventricles contract next

Question 2

What is a key difference between cardiac muscle and skeletal muscle?

Answer 2

Every myocyte contracts for every beat (all or non TISSUE response)
Skeletal muscles have altering number of cells that contract

Question 3

What are the phases of the cardiac action potential?

Answer 3

Phase 0 = Upstroke (Na channels or T-type Ca in SA/AV nodes)
Phase 1 = repolarization (inactivation of Na and opening of transient outward K)
-spike is an overshoot seen in ventricular and purkinje fibers but not in SA/AV nodes
Phase 2 = plateau (Ca slowly inactivating while K+ channels slowly activating)
-protects heart from extra excitation (tetany)
-due to calcium channels
-not seen in skeletal muscle
Phase 3 = rapid repolarization (inactivation of Ca and activation of K)
Phase 4 = Resting potential (inward rectifier)

Question 4

What is the significance of phase 2?

Answer 4

Controls contraction and guards against dangerous arrhythmias

Question 5

What dictates the membrane potential?

Answer 5

By whichever ion is most permeable at rest
As determined by the Nernst equation…
E = (61.5/z)*log (Io/Ii)

Question 6

How many ways can the channels get blocked?

Answer 6

In two ways

1. The channel can be physically closed
2. An inactivation gate (the ball and chain) could close in on it as well

Question 7

What are the key characteristics of the Na+ channel ?

Answer 7

It mediates the upstroke (stage 0)
Has two gates (an activation and inactivation gate)
Inactivation gates are closed as you get more depolarized
Na channel gets blocked by tetrodotoxin

Question 8

What does tetrodotoxin do?

Answer 8

They block Na channels

Question 9

What are the consequences of a raised extracellular K+?

Answer 9

More positive the membrane potential = more inactivation gates that are CLOSED so therefore the upstroke is shorter because less Na channels would be open
Shorter upstroke = slower conduction and possibly no contraction (see curve f)
Causes arrhythmias and perhaps death

Question 10

What are the key characteristics of the T-type Ca channel?

Answer 10

Stands for “Transient” type calcium channel
Activates between -80 to -40mV
Found only in SA and AV nodal cells that help generate spontaneous action potentials
So t-type Ca channels are crucial to generation of phase 0 in SA and AV nodal cells
Blocked by Amiloride
Less sensitive to dihydropyridine blockers

Question 11

What are the key characteristics of the L-type Ca channel?

Answer 11

Stands for “Long” lasting type calcium channel
Activates between -30mV to 0 mV
Responsible for the PLEATEAU (phase 2) of the cardiac action potential
Blocked by the following antagonists:
i. Nifedipine (dihydropyridine)
ii. D600
iii. diltiazem

Question 12

What are the key characteristics of the INWARD RECTIFIER K+ current?

Answer 12

It is called “inward” because under EXPERIMENTAL conditions, K+ was able to be carried inwards…but this would never occur PHYSIOLOGICALLY
In physiologic conditions, K moves out of the cell

Question 13

What is the significance of the inward rectifier K+ channel?

Answer 13

Responsible for the major proportion of RESTING potential
Stage 4
Channel deactivates at potentials above -20mV (so it is off during the plateau

Question 14

What are the key characteristics of the DELAYED K+ channel?

Answer 14

Activates very slowly during positive potential
Responsible for gradual repolarization during plateau
Stage 2 to Stage 3!

Question 15

What is the point of the transient outward current?

Answer 15

Produces a little dip between phase1 and 2

Potassium type channel

Question 16

Is the fast or slow response sensitive to TTX? D600?

Answer 16

Fast response is sensitive to TTX (Na)

Slow response is sensitive to D600 (Ca)

Question 17

What happens if you block Na channels with TTX? Ca channels with D600?

Answer 17

If you block Na, Ca can carry the AP
If you block Ca, Na can carry the AP
Calcium and sodium channels are both capable of generating an AP alone
So depending on the tissue, you can have different channels generating an AP
This is why different tissues have different looking AP’s!!

Question 18

What is the difference between the Na and Ca current?

Answer 18

Na is FAST (“rapid”)

Ca is slow

Question 19

In what myocytes are the slow Ca channels responsible for upstroke (stage 0)?

Answer 19

SA and AV nodes

Na current is not operative in SA and AV nodes because potentials are not sufficiently negative

Question 20

In which myocytes are the rapid Na channels mainly responsible for upstroke?

Answer 20

Ventricles
Atrium
Purkinje fibers
Bundle of His
Ca can also contribute but are overshadowed by the speed of the Na channel

Question 21

What are the causes of Long QT syndrome?

Answer 21

What are the causes of Long QT syndrome?
Genetic (K+ channels are blocked)
Drug induced (K+ channels are blocked)
Too many sodium channels
Prolongs the Ventricular depolarization
If the plateau lasts too long, repolarization can be adversely affected and torsades de pointes could occur

Question 22

What two categories can the action potentials of the heart be divided into?

Answer 22

1. Contractile AP (atrial and ventricular)

2. Conduction AP (SA node)

Question 23

What are the currents responsible for SA node?

Answer 23

1. DIASTOLIC potential = I_k (as the K+ channels switch off, this shit depolarizes)
2. I_f = funny current (both K and Na are permeable) and also depolarizes
3. I_ca = depolarization

Question 24

What is diastolic potential?

Answer 24

The term for the “resting” potential of SA nodes but as Goldman states, stage 4 is not flat, so diastolic is used instead

Question 25

What is one way to change the identity of the pacemaking myocyte?

Answer 25

By inactivating some K+ channels to make ventricle myocytes contract the fastest

Question 26

How does AP propagate?

Answer 26

Through gap junctions
Cardiac muscle = functional syncytium (or functionally share the same cytoplasm, even each cell have own nuclei, so not true syncytium)