Anatomy and Electrical Activity

Question 1

Where does the heart reside?

Answer 1

in the thorax (thoracic cavity)

Question 2

region within the thorax between the right and left pulmonary cavities

Answer 2

mediastinum

Question 3

Things that reside within the mediastinum:

Answer 3

heart 
pericardial sac 
trachea 
bronchi 
esophagus 
thymus 
neurovasculature

Question 4

Two layers of the pericardium:

Answer 4

Parietal pericardium:
• outermost fibrous layer

Visceral pericardium:
• inner serous layer

*space between the layers is filled with fluid secreted by the serous layer

Question 5

Functions of the pericardium:

Answer 5

1. ) protects the heart from chest infections and abrasions
2. ) fixes heart in the mediastinum
3. ) prevents excess blood engorgement

Question 6

an excess accumulation of fluid between the layers of the pericardium

Answer 6

tamponade

Question 7

muscular pouch (appendage) in the upper corner of the atria

Answer 7

auricle

Question 8

Layers of heart muscle:

Answer 8

endocardium (inner lining)
myocardium (heart muscle)
epicardium (outer surface)

Question 9

Cardiac vs skeletal muscle

Answer 9

Cardiac
• involuntary
• autorhythmicity
• AP initiated in heart in specialized muscle cells
• RMP = -90 mV
• duration of AP = 300 msec
• 5 phases of the AP
• functions as syncytium (group contraction)
• needs extracellular Ca++ for contraction

Skeletal 
• voluntary 
• no autorhythmicity  
• dependent on ACh for AP 
• RMP = -85 mV 
• duration of AP = 2.5 msec 
• 3 phases of the AP 
• doesn't function as a syncytium 
• doesn't need extracellular Ca++ for contraction 

Similarities:
• both striated
• both have same contractile processes

Question 10

term for coordinated contraction as a unit

Answer 10

syncytium

Question 11

AP of skeletal muscle vs AP of cardiac muscle

Answer 11

Skeletal muscle: Single AP lasts 2.5 msec. It largely involved changes in Na+ (depolarization) and K+ (repolarization) permeability.

Cardiac muscle: AP lasts much longer and has more phases. Skeletal muscle lacks phase 1 (transient repolarization) and phase 2 (plateau). The duration of the AP allows enough time for excitation-contraction coupling, with full force of contraction.

Question 12

specialized muscle cells involved in the initiation and propagation of APs (have little mechanical ability); allows excitation to originate within the heart itself

Answer 12

conductile cells

*don’t contribute to the forceful contraction of the heart

Question 13

Describe the steps of the electrical conduction within the heart.

Answer 13

1. ) The SA node is the pacemaker of the heart, located in the right atrium (near the vena cava). This cluster of conductile cells is where APs originate and conduct the signal to atrial muscle and internal fibers.
2. ) The signal gets here from the SA node via internodal fibers. The AV node is located in the inter-atrial septum. It relays and delays the depolarization wave from the atria to the ventricles. This delay is due to the slow conduction of AV cells, allowing the atria to contract before the ventricles.
3. ) The bundle of His divides into left and right branches to transfer the depolarization wave to the left and right ventricles.
4. ) The purkinje fibers are interwoven among contractile cells, allowing for very rapid conduction of APs. This allows the ventricular muscles to contract in unison.

Question 14

In the electrical circuit of the heart, what connects the SA node to the AV node and to the left and right atria?

Answer 14

internodal fibers

Question 15

small, Purkinje-like conductile cells

Answer 15

internodal cells

Question 16

What is the fastest step in the electrical activation of the heart? Slowest?

Answer 16

Fastest: bundle branches –> purkinje network

Slowest: AV node

Question 17

It the probation of impulses faster in the endocardium or epicardium?

Answer 17

endocardium

Question 18

muscle cells that constitute most of the atria and ventricles; account for mechanical contraction of the heart

Answer 18

contractile cells

Question 19

regions of the cell membrane that make contact between adjacent myocytes; comprised of gap junctions

Answer 19

intercalated discs

Question 20

low resistance connections in intercalated discs that allow ions to readily flow between cells; electrically couple neighboring cells

Answer 20

gap junctions

Question 21

What does gap junction density account for?

Answer 21

different conduction velocities

Purkinje > contractile > SA node > AV

Question 22

part of a contractile cell that carries APs into the cell, continuous with the SR at the cisterna

Answer 22

T-tubules

Question 23

T-tubules in skeletal muscle vs cardiac muscle

Answer 23

Skeletal muscle:
• 2 T-tubles per sarcomere
• shorter diffusion distance for Ca++

Cardiac muscle
• 1 T-tubule per sarcomere
• T-tubule volume is 25x greater in cardiac muscle

Question 24

the basic unit of a striated muscle (region between two Z lines)

Answer 24

sarcomere

Question 25

Describe the AP in conductile vs contractile cells.

Answer 25

Conductile cells: • SA nodal cell • less negative resting potential • less stable resting potential due to increased leakiness to Na+ and Ca++ • slower developing AP due to inactivated fast Na+ channels, but open slow Na+ channels • Na+ dependent increase in resting potential elicits AP at threshold potential (-40 mV) • self-excitability that accounts for intrinsic rhythmicity Contractile cells: • Purkinje, atrial, and ventricular cell • more negative and stable resting potentials • more rapid depolarization with prominent plateau due to fast Na+ channels

Question 26

cells that control HR

Answer 26

pacemaker cells

Question 27

the normal pacemaker of the heart

Answer 27

SA node

Question 28

Characteristics of the SA node:

Answer 28

* exhibits progressive depolarization during the resting phase of an AP ("pacemaker potential") * cells in the SA node are intrinsically leaky to Na+ * generates a cardiac rhythm of 60-100 bpm

Question 29

How is the AV node and Purkinje fibers latent pacemakers?

Answer 29

The AV node and Purkinje fibers exhibit a natural self-excitatory discharge rate. Since the discharge rate of the SA node is greater than both the AV node and the Purkinje fibers, impulses from the SA node discharge the AV node and Purkinje fibers before self-excitation can occur.

Question 30

The heart muscle itself doesn't have a discharge rate unless it is injured. What is this called?

Answer 30

ectopic pacemaker

Question 31

a common site for conduction block in heart disease

Answer 31

AV bundle In terms of discharge rate, the SA node will always win out unless there is a block between the atria and ventricle. When this block occurs, the atria beat at the SA node rate but the ventricles will beat an an ectopic rate.

Question 32

Two big factors that are involved in the regulation of HR:

Answer 32

Sympathetic nerves (catecholamines) increase HR--> norepinephrine Parasympathetic nerves (acetylcholine) decrease HR.

Question 33

How do sympathetic nerves increase HR?

Answer 33

* increase the slope of the pacemaker potential by making it even more leaky to Na+ (increase in Na+ permeability) * reduces the time it takes to reach threshold potential

Question 34

How do parasympathetic nerves decrease HR?

Answer 34

* hyperpolarize pacemaker cell membrane by increasing K+ permeability via muscarinic cholinergic receptors * reduce the slope of the pacemaker potential * longer time required to reach threshold potential

Question 35

What happens during syncope (fainting)?

Answer 35

intense vagal stimulation can reduce HR to zero (faint) --> the heart escapes --> switches to AV node or Purkinje pacemaker (sympathetic) --> lowers HR

Question 36

Five phases of the normal cardiac AP:

Answer 36

``` Phase 0: upstroke (depolarization) Phase 1: partial repolarization Phase 2: plateau Phase 3: repolarization Phase 4: resting potential ```

Question 37

What does an AP result from?

Answer 37

the opening and closing of highly selective and voltage-sensitive ion channels in the cardiomyocyte alters membrane permeability, intracellular ion concentrations, and the TMP, yielding the AP

Question 38

The movement of ions across the sarcolemma is determined by...

Answer 38

its chemical (concentration) gradient and electrical potential

Question 39

the electrical potential difference (voltage) between the inside and outside of a cell

Answer 39

transmembrane potential (TMP)

Question 40

What determines TMP?

Answer 40

the difference in ion concentration inside vs outside the cell

Question 41

What produces a more positive TMP? Negative?

Answer 41

The net ENTRY of positive ions into a cell produces a more positive TMP. The net EXIT of positive ions out of the cell yields a more negative TMP.

Question 42

Phase 0: Upstroke

Answer 42

* AP from SA node opens fast Na+ channels causing an increase in Na+ permeability * dramatic reduction in K+ conductance (prevents repolarization)

Question 43

Phase 1: Partial Repolarization

Answer 43

* closure of fast Na+ channels * opening of K+ channels * membrane potential begins to fall (partial repolarization)

Question 44

Phase 2: Plateau

Answer 44

* despite closure of fast Na+ channels, potential remains positive or near 0 for about 300 msec * due to the opening of voltage-gated slow Ca++ channels * Ca++ influx and Na+ influx from slow Na+ channels maintain plateau * slow leakage of K+ out of cell keeps potential from rising

Question 45

Phase 3: Repolarization

Answer 45

* increased K+ conductance | * inactivation of slow Ca++ and Na+ channels

Question 46

Main contractile elements of cardiomyocytes:

Answer 46

Myosin: thick filaments with globular heads, contain myosin ATPase Actin: smaller molecule (thin filaments), woven between myosin filaments

Question 47

Regulatory elements of contraction:

Answer 47

Tropomyosin: lies in the groove between actin filaments, prevents contraction in the resting state by inhibiting the interaction between myosin heads and actin Troponin: complex (3 subunits) located along the actin strands, regulates the contractile process by binding Ca++

Question 48

cardiomyocyte contractile cycle

Answer 48

1. ) Ca++ binds to troponin C, leading to a conformational change that displaces tropomyosin from the actin binding sites. 2. ) Crossbridge formation occurs with ATP hydrolization into ADP + P. 3. ) Power stroke moves actin filament toward the center of the sarcomere. ADP + P are released from the myosin heads. 4. ) Actin is released with ATP binding to myosin. Myosin heads cocked back into firing position ready to make crossbridges further downstream. 5. ) Cycle continues until cellular Ca++ levels decrease, allowing Ca++ to dissociate from troponin. Tropomyosin returns to its original conformation that blocks actin binding sites.

Question 49

How is excitation-contraction coupling in cardiomyocytes mediated by Ca++?

Answer 49

* Ca++ entering the cell during the plateau phase (systole) triggers the release of Ca++ from the SR— small fraction of total SR Ca++ * Troponin C (on actin) binds elevates cytotoxic Ca++ to enhance the formation of cross-bridges between actin and myosin and elicits contraction—Ca++ not sufficient to bind all troponin sites; more Ca++ release = increased contractility (unlike skeletal muscle wherein all troponin sites bind Ca++)

Question 50

What mediates the release of Ca++ from the SR after phase 2 Ca++ enters?

Answer 50

ryanodine receptors (Ca++ gated Ca++ channels) on the SR *ryanodine = toxin that blocks contraction by preventing Ca++ release from the SR

Question 51

During diastole, how is Ca++ removed from the cytosol?

Answer 51

1. ) SERCA (sarco-endoplasmic-reticulum Ca++-ATPase) pumps Ca++ into SR 2. ) Sarcolemmal Na+/Ca++ exchanger removes Ca++ from the cell (relatively small amount compared to 1)

Question 52

How does increased contractility affect the strength of contraction?

Answer 52

increased contractility = muscle contraction with greater force at given muscle length • troponin-binding sites not all saturated by elevated cytosolic Ca++ levels associated with normal AP • stimuli for enhanced Ca++ release from the SR will increase troponin sites that bind Ca++, leading to increased force generation by muscle

Question 53

Modulators of cardiac contractility:

Answer 53

* stimulation frequency | * catecholamines

Question 54

effect of stimulation frequency on contractile strength (positive staircase effect)

Answer 54

increasing the frequency of stimulation increases the amount of Ca++ entry and shortens the time available for Ca++ removal by the exchanger (thereby increasing contractile strength)

Question 55

effect of catecholamines on contractile strength

Answer 55

β1-adrenergic receptor activation by catecholamines --> increases cAMP/PKA --> makes more Ca++ available for release with subsequent APs by: - opening L-type Ca++ channels in the sarcolemma - increase activity of SERCA *net effect = more Ca++ available for troponin on myofilaments