Cardiac Excitation and Contraction I

Question 1

Cardiac output vs Stroke volume vs Ejection fraction

Answer 1

CO: blood volume pumped by the heart in 1 min (~5L/min)

SV: blood volume ejected by left ventricle in 1 contraction (70mL)

EF: fraction of blood volume in left ventricle ejected in 1 contraction (60%)

Question 2

Effective Refractory period (ERP)

Answer 2

Time period after an action potential (or QRS complex) during which the heart is refractory to another action potential

Question 3

SA node

Answer 3

• In the upper right atrium
• Highest level of automaticity; “sets the pace” for heart rate

Question 4

AVN / AV node

Answer 4

• Between the atria & ventricles
• Slow conduction & behaves like an electrical filter during high atrial rates (e.g. atrial fibrillation
• Conduction here is mediated by L-type Ca current

Question 5

Bundle of His & Bundle branches

Answer 5

Extends from distal end of the AV node & divides into smaller bundle branches in the ventricles, terminating in Purkinje fibers.

Specialized for rapid conduction of cardiac APs

Question 6

Purkinje fibers

Answer 6

Specailized cardiac cells that spread out over the inner surface of the ventricles (endocardium).

Weakly contract, but are mostly specialized for rapid conduction of APs to the ventricular muscle.

Question 7

The ___ is where the AP originates to stimulate heart contraction.

___ is specialized for slow conduction and prevents ventricles from being paced faster than they can fill with blood when atrial tachyarrhythmia occurs.

___ are specialized for rapid conduction & delives AP to the inner ventricular myocardium (nedocardium) via a web-like network of Purkinje fibers.

Answer 7

SA node- pace setter

AV node- slow conduction & prevents ventricles from pacing faster than they can fill during atrial tachyarrhythmia

His bundle- rapid conduction & delivery of APs to ventricles

Question 8

Why do the ventricles have thicker walls (esp the left) than the atria?

Answer 8

They pump blood out of the heart into the rest of the body in systole

Question 9

Steps of normal sinus rhythm

Answer 9

1. Spontaneous apperance of APs in the SA node
2. Spread of AP rapidly through the atria and into the AV node
   
   1. Slow conduction of AV node gives the atria time to contract and fill the ventricles
3. AP reaches bundle of His, which divides into the left & right bundle branches on each side of the ventricular septum going toward the apex
4. Divide into smaller Purkinje fibers that spread out all over the ventricular endocardium
   
   1. Conduction through HIs-Purkinje system is so fast that it basically simultaneously stimulates all muscle cells in both chambers

Question 10

Intercalated discs between cardiac muscle fibers

Answer 10

Group of gap junctions between myocardial cells, allowing

• excitation to spread through cardiac muscle in the direction that muscle fibers are oriented.
• spread of metabolic or second msger signals btwn cells

Question 11

Gap junctions of intercalated discs can “close” under conditions commonly produced during ____

Answer 11

myocardial ischemia

chronic depolarization of neighboring cells (depolarized resting potentials)

acidic conditions

high Ca_i

Question 12

P wave

Answer 12

Atrial depolarization

Question 13

PR interval

Answer 13

Delay in conduction that takes place in the AV node

Question 14

QRS complex

Answer 14

Ventricular depolarization

Q wave: initial depolarization of septum before the ventricles

Question 15

Things that widen the QRS complex (affects normal srpead of ventricular depolarization)

Answer 15

Na channel blocking drugs

Myocardial ischemia

Hyperkalemia

Question 16

T wave

Answer 16

Ventricular repolarization

Question 17

QT interval

Answer 17

time for complete ventricular repolarization

Question 18

things that lengthen the QT interval

Answer 18

K-channel blocking drugs

Mutations in ion channels

long QT syndrome

Question 19

Events that prolong the QT interval are typically proarrhythmic:

Answer 19

They increase the likelihood for multifocal ventricular arrhythmias such as Torsades de pointes –> life threatening

Question 20

SAN, AVN, and Purkinje fibers all display

Answer 20

automaticity: ability to spontaneously depolarize an action potential

Demonstrated by the phase 4 depolarization

Question 21

Action potentials in the SAN and AVN both have slow upstroke velocity caused by

Answer 21

L-type Ca current

Question 22

The upstroke of APs in cells outside of the node

Answer 22

Na current

Question 23

The 5 phases of a cardiac action potential

Answer 23

Question 24

Why do different regions of the heart show differently shaped action potentials?

Answer 24

Cells in different regions express varying densities of the various ion channels that regulate the shape of the cardiac action potential

Ex) Atrial cells’ APs are much faster due to differences in ion channel expression

Question 25

What ion channel is responsible for phase 4 when cardiac cells are left unstimulated?

Answer 25

The K-selective channel opens, producing an **inwardly-rectifying K current** called **I_K1** K ions leave the cell, but as they leave, other ions get stuck in the channel and block K+ efflux

Question 26

What ion channel is responsibnle for phase 0?

Answer 26

**Na channels** transiently opening while K channels are closed

Question 27

What maintains the plateau phase of the ventricular action potential (**phase 2**)?

Answer 27

I_to's repolarizing effect is slowed by * Activation of an **L-type Ca current (I_Ca)** causing Ca influx * Inactivates slowly * There's a small (~1%) fraction of Na channels that don't fully inactivate after depolarization

Question 28

what is responsible for phase 1?

Answer 28

**I_to**: transient K efflux produces rapid repolarization

Question 29

What's responsible for the **rapid repolarization of phase 3**?

Answer 29

* Slow inactivation of the Ca current * Activation of additional outward K currents **(I_Kr & I_Ks)**

Question 31

The resting potential is a function of ____ concentration

Answer 31

extracellular K concentration

Question 32

**Hyperkalemia** causes ______ of the resting potential

Answer 32

**Depolarization** Hyperkalemia may result from * **Renal failure** * **Addison's disease (adrenal gland destruction)** * **K-sparing diuretics**

Question 33

How does **myocardial ischemia** cause a **depolarization of the resting potential**?

Answer 33

Occlusion of a coronary artery will produce local tissue hyperkalemia

Question 34

**Relative refractory period (RRP)**

Answer 34

time after the ERP during which conduction occurs, but at a **less than maximal velocity bc not *all* Na channels have recovered** from inactivation yet Beats originating during the RRP have a **slower upstroke velocity** and produce a **wider QRS** complex

Question 35

Avg resting heart is 70 bpm **Sympathetic nerves** innervate the \_\_; whereas, **vagal nerves** innervate the \_\_\_

Answer 35

Sympathetic innervates **atria & ventricles** Vagal nerves innervate only the **atria, SA node, AV node,** and **Purkinje fiber system**

Question 36

Depolarized resting potentials are common in cells exposed to **severe stretch** (opens non-selective ion channels) , **hyperkalemia**, or **ischemia.** Depolarized resting potentials has what impact on the Na current?

Answer 36

**Na channel inactivation** * Reduces Na current amplitude * Slower action potentials (may even block conduction) _{note: "rested"=available to be opened}

Question 37

Impact of neural stimulation on * heart rate * AV node ERP, * PR * contractility (SV)

Answer 37

note: vagal stimulation has little impact on contractility

Question 38

**Right** vs **left vagal nerve**

Answer 38

**Right** affects **SA** **Left** affects **AV**

Question 39

Sympathetic stimulation: **Norepinephrine** binds to ____ receptors \>\_\_\>\_\_\>\_\_\>\_\_\_ phosphorylates the L-type Ca channel to allow Ca influx. Parasympathetic: **Acetylcholine** binds to __ receptors \>\_\_\_\> inhibits ___ & activates a \_\_\_

Answer 39

* SYMP: Norepi * \> **G_s** * \> **adenylate cyclase** * \> **cAMP** * \> **PKA** phosphorylates L-type Ca channel * PARASYMP: Ach * \> **type 2 muscarinic receptors** * \> **G_i** * \> inhibits **adenylate cyclase** and activates a **K** **channel** resulting in K efflux (I_KAch)

Question 40

Why do cells at the nodes have a l**ess negative diastolic membrane potential** and **slower upstroke velocity in phase 0** than atrial or ventricular cells?

Answer 40

**Lower K+ permeability** -\> smaller I_K1 -\> less negative RP Conduction is primarily **Ca current-mediated** -\> slower upstroke velocity because the **Ca current is much smaller than the Na current**

Question 41

How does Ach prolong the AV node ERP?

Answer 41

**Increasing K conductance & Decreasing Ca conductance** --\> AV node cell will have to wait more time for enough Ca channels to regain their excitability for conduction

Question 42

Latent pacemakers Ectopic pacemakers

Answer 42

**Latent pacemaker**: Cells outside the SAN that can become pacemakers If SAN's automaticity becomes depressed or cells outside the SAN become enhanced, then the region that starts generating APs outside the SAN is the **ectopic pacemaker**. AVN or Purkinje

Question 43

bpm of san, avn, and purkinje

Answer 43

SAN = 70bpm (impacted by autonomics) AVN= 40-60 bpm Purkinje = 15-40 bpm

Question 44

What is I_f?

Answer 44

funny, nonselective current that *slowly* activates upon _hyperpolarization_ below a threshold of -50mV. -\> Na primarily enters ( depolarizing)

Question 45

What are the sources of depolarizing current **during diastole** **(phase 4)** in the SAN & Purkinje fibers?

Answer 45

* SAN * Both T- and L-type Ca currents * I_f * _​​​Purkinje * Just If

Question 46

**Ivabradine** blocks If, thus __ the heart rate. **L-type Ca channel blockers** will __ the heart rate due to their affect on \_\_\_.

Answer 46

Ivabradine reduces the heart rate L-type Ca channel blockers also **reduce** HR thru their affect on the **SAN** (butalso by slowing conduction thru AV); can even cause bradycardia or asystole

Question 47

Vagal stimulation vs Sympathetic stimulation on the slope of the **phase 4 depolarization**

Answer 47

Vagal stimulation -\> greater K efflux in SAN & Purkinje --\> **less steep slope** Symp stimulation -\> greater L-type Ca current & If -\> **steeper slope**

Question 48

How does **hypo**kalemia result in development of an ectopic pacemaker activity?

Answer 48

Lowering [K]_out causes **E_K** and the **maximum diastolic potential** to be **more negative.** **-**\> **Activates more I_f** and **r****educes I_KI** **--\> Enhances phase 4 depolarization in Purkinje** (strong K permeability)

Question 49

What **Ca channels** are the trigger for the SR to release its Ca into the cytoplasm? What is the mechanism?

Answer 49

It's the calcium from the **L-type Ca channels** participating in **calcium-induced calcium release**: 1. **Ca influx** **during AP plateau triggers the release of SR's Ca** into the cytoplasm. 2. Large **rise in free cytosolic Ca activates contraction** of the myofilaments (systole). 3. Relaxation (**diastole) occurs following** the 1. reuptake of cytosolic Ca into the SR via **SERCA** 2. extrusion of Ca into the extracellular fluid via **Na/Ca exchange.**

Question 50

**Excitation-Contraction Coupling**

Answer 50

Infux of Ca from AP triggers release of Ca from the SR into the cytoplasm --\> contraction Reuptake of cytosolic Ca into the SR via **SERCA** and into the extracellular fluid via **Na/Ca exchange** --\> relaxation

Question 51

The more Ca released into the cytoplasm (e.g. B-adrenergic agonists), the increased

Answer 51

force of contraction

Question 52

Contractility in cardiac tissue is sensitive both tot he amt of Ca influx, which regulates Ca-induced Ca released from the SR, as well as ___ because \_\_\_

Answer 52

intracellular & extracellular Na concentrations due to the role of the Na/Ca exchanger in clearing out the Ca afterwards