Cardiac muscle cells

Question 1

Cardiac muscle cells are connected together with ____________ in order to form what is called electrical syncytium so that electrical signals can easily pass from one cell to another.

Answer 1

gap junctions

Question 2

-This electrical syncytium allows an ___________ that starts in one point of this syncytial organ to quickly cross all the organ. Although cardiac muscle cells are striated cells, the heart is not under the voluntary control, you cannot stop beating your heart

Answer 2

action potential

Question 2

Abundance of mitochondria provide great _________ capacity

Answer 2

oxidative

Question 3

Heart is formed by ___ syncytia (undistinguishable):

Answer 3

2
Atrial syncytium- composed by the walls of the 2 atria

Ventricular syncytium- composed by the walls of the 2 ventricles

Question 3

The skeletal muscle is able to contract even in the absence of ___________________, but the cardiac muscle cannot. This is because SR calcium release is dependent on extracellular calcium influx.

Answer 3

extracellular calcium

Question 4

cardiac muscle cells are _________ than skeletal muscles cells in terms of size

Answer 4

smaller

Question 5

The sarcoplasmic reticulum of cardiac muscle has the ___________, which are connected with the extracellular space and allow the electrical action potential to reach the deepest parts of the cardiac muscle

Answer 5

T tubules

Question 5

Atria and ventricles are separated by some _________ tissue.

Answer 5

fibrous, This fibrous tissue surrounds also the 2 atrioventricular valves

Question 5

Cardiac muscle contains a ________ amount of connective tissue than skeletal muscle and smooth muscle

Answer 5

higher.
It seems that this overexpression of connective tissue in the heart is mainly to avoid muscular rupture and overstretching of cardiac muscle cells. The cardiac muscle relies on a higher elastic response to stretching. Skeletal muscles can tolerate a greater degree of stretching and the reason of this higher toleration is probably due to the fact that the stretching of skeletal muscles is limited by the joints of the bones. Instead, the heart has not any joints and for this reason the cardiac muscle expresses more connective.

Question 5

They are strictly interconnected by _____________, which are structures that are composed by a combination of mechanical connections and gap junctions. These intercalated discs are involved in the transmission of electricity and mechanical movements

Answer 5

intercalated discs

Question 6

______________ extends along the length of actin filaments and it serves as a scaffold for the thin filaments.

Answer 6

Nebulin

Question 6

____________anchors actin to Z lines

Answer 6

Alpha-actinin

Question 6

____________ regulates the length of thin filaments

Answer 6

Tropomodulin

Question 7

____________ anchors thick filaments to the Z-lines in order to prevent overstretching of sarcomere. Largest protein contained in the human body.

Answer 7

Titin

-Titinopathies- recent studies have shown that titin is probably involved in regulatory functions- titin is involved in some signaling pathways among the different cardiomyocytes. Genetic defects about this protein can result in atrophy and this is true for both cardiac muscle and skeletal muscle cells. In the case of cardiac muscle cells, this atrophy can lead to cardiac dysfunctions called titinopathies, that can also cause death.

Question 8

In the heart, the ________________ are located in the sinoatrial node, which is located in the right atrium. The pacemaker cells generate 70 electrical stimulations per minute (heartbeat). All of these stimulations are able to propagate through a conductive circuit (gap junctions).

Answer 8

pacemaker cells

Question 8

The _________________ are the cardiac cells that show the fastest spontaneous depolarization.

Answer 8

sinoatrial node

The sinoatrial node generates a depolarisation that reaches a level of depolarisation sufficient to cause the depolarisation of other cardiac muscle cells. Once an action potential is generated in the sinoatrial node, in order to reach the ventricles, it passes through atrioventricular valves and after that it reaches the atrioventricular node and then it can pass through the ventricles thanks to a dedicated transmission pathway formed by the bundle of His and the Purkinje fibers

Question 9

The contraction of the cardiac muscle lasts _____ milliseconds

Answer 9

300

Question 10

The action potential can pass throughout the atria within approximately 70ms, while it crosses the entire heart in ___________ milliseconds

Answer 10

220

Question 11

When an action potential passes over the cardiac muscle membrane, the action potential spreads along the T tubules and starts to act on the membrane of T tubules and this interaction results in the release of _______________ by the sarcoplasmic reticulum

Answer 11

calcium (Ca2+)
The calcium (Ca2+) released diffuses in the myofibrils and promotes the chemical reaction that stimulates the interaction among actin and myosin filaments producing the muscle contraction.

Question 11

Calcium ions are not released only by the _______________, but they also diffuse within cardiac muscle cells through ___________thanks to the action potential that causes the opening of voltage dependent Ca2+ channels, that are located in the membrane of T tubules. Extracellular concentration of Ca2+ is fundamental for cardiac muscle cells.

Answer 11

sarcoplasmic reticulum, T tubules

Question 12

Strength of the contraction of cardiac muscle cells depends on __________________

Answer 12

the concentration of calcium in the extracellular fluids

Question 12

The longer duration of the action potential of cardiac muscle cells is the result of a slow but continuous flow of ______ entering cardiac muscle cells through voltage-gated L-type Ca2+ channels, localized in the sarcolemma. Calcium entering the cell activates calcium release channels, known as ryanodine receptor channels (RYR) triggering the release of Ca2+ into the cytoplasm from the SR.

Answer 12

Ca2+

Question 13

In the absence of _______________, an action potential can still be initiated in the cardiac muscle cells although it is considerably shorter in duration and it is unable to initiate the contraction of cardiac muscle cells. The influx of extracellular Ca2+ is really important for triggering the release of Ca2+ by the sarcoplasmic reticulum and therefore for initiating the contraction of cardiac muscle cells.

Answer 13

extracellular Ca2+

Question 13

___________________________ mainly formed by 5 subunits, alpha-1, alpha-2, beta, gamma and delta (α1, α2, β, γ, and δ). Alpha-1subunit is called dihydropyridine and it is the dihydropyridine receptor (DHPR). Although the alpha-1 subunit is present both in cardiac and skeletal muscle, it plays different functions in these 2 types of muscles.

Answer 13

L-type Ca2+ channels (cardiac muscle cells)

Question 13

The terminal regions of the cardiac sarcoplasmic reticulum are rich in ________________, which are involved in the flow of Ca2+ inside cardiac muscle cells

Answer 13

RyRs (ryanodine receptors)

Question 14

The sarcoplasmic reticulum of _______________ contains more Ca2+ than the sarcoplasmic reticulum of skeletal muscle.

Answer 14

cardiac muscle

Question 14

The difference in ______ dependency between cardiac muscle and skeletal muscle relies on the dihydropyridine receptor (DHPR) isoform expressed in cardiac muscle cells.

Answer 14

Ca2+
Cardiac DHPR can promote the contraction of muscle only if there is extracellular Ca2+. Skeletal muscle expresses another isoform of DHPR, which not depends on extracellular Ca+2 and contract also in the absence of extracellular Ca2+.

Question 15

The activation of ____________________ causes a longer duration of action potential in cardiac muscle, compared to skeletal muscle, and causes also a longer refractory period. This is a mechanism used by the heart to avoid continuous contraction of cardiac muscle. In this way, the force of contraction of cardiac muscle is modulated

Answer 15

voltage-gated L-type Ca2+ channels

Question 15

In a cardiac muscle cell in vitro, a simple way to modulate the force of contraction is to modify the ___________ concentration. Higher extracellular Ca2+ concentration corresponds to higher tension, while lower extracellular Ca2+ corresponds to lower tension. The decrease of the force of contraction is not associated with the duration of contraction of cardiac muscle because the velocity at which Ca2+ is removed from the sarcoplasmic reticulum is not affected by extracellular Ca2+.

Answer 15

extracellular Ca2+

Question 15

Beta-adrenergic receptors located on the cardiac muscle cells are activated by __________, which is produced by sympathetic nervous system.

Answer 15

epinephrine

Question 15

The activation of _____________receptors- Increases of heart activity:

Answer 15

beta-adrenergic

Question 16

Positive __________- increases the intracellular Ca2+ concentration leading to a more forceful contraction.

Answer 16

inotropy

Question 16

Positive _______________- increase of the rate of relaxation with a shorter contraction

Answer 16

lusitropy

Question 17

Positive ____________- increases the frequency of heart contractions

Answer 17

chronotropy

Question 17

The phosphorylation SERCA is mediated by the __________

Answer 17

PKA (kinase).

Question 17

Phospholamban- when phosphorylated:

Answer 17

it relieves its inhibitory effect on SERCA, enhancing the pump’s ability to transport calcium ions back into the sarcoplasmic reticulum. This increase in calcium uptake promotes muscle relaxation and improves cardiac contractility.

Question 18

At the end of this processes, the sarcoplasmic reticulum accumulates more Ca2+ thanks to the deactivation of ____________________and there is also a bigger release of Ca2+ into the sarcoplasm thanks to the action of ryanodine receptors (RyRs).

Answer 18

phospholamban proteins (PLN proteins)

Question 19

Sympathetic stimulation also increases heart rate through a direct effect on the ___________

Answer 19

pacemaker cells

Question 19

_____________________ is an arrhythmic syndrome that can also lead to death in children

Answer 19

Catecholaminergic polymorphic ventricular tachycardia CPVT

CPVT is an inherited autosomal dominant disease associated with mutations in the cardiac ryr2. This genetic defect causes an increase in Ca2+ release from the sarcoplasmic reticulum, compared to the normal condition. During exercise, an increased intracellular Ca2+ concentration (combined effects of β-adrenergic stimulation and increased activity of the mutated RYR2) promotes delayed afterdepolarizations (arrhythmias). This means that cardiac muscle cells contract even when they should be relaxed.

Treatment of CPVT involves antiadrenergic therapy (β-adrenergic antagonists) or, for unresponsive patients, an implanted defibrillator

Question 20

_____________ of the heart- the ability of the heart to increase its force of contraction when stretched.

Answer 20

Frank-Starling law

According to this law, this phenomenon happens every time that the venous blood return is increased. The importance of this process is that this mechanism enables the heart to pump whatever volume of blood it receives. The more blood is received by the heart, the more the heart is able to pump out blood since more force of contraction is developed

Stretching of the heart increases also the passive tension of the cardiac muscle, that is to say the response due to the elastic properties of the organ and intracellular elastic proteins (titin).

Question 21

_____________ cells more sensitive to calcium, are able to contract with lower concentrations of extracellular calcium and develop more force

Answer 21

Cardiac muscle

Question 21

Cardiac muscle converts chemical energy into mechanical energy, which is necessary for contraction. Approximately 70% of this energy derives from ___________________

Answer 21

oxidative metabolism

In order to obtain this 70% of energy, it involves mainly the metabolism of fatty acids. The remaining 10-30% comes from glucose and lactate. Since myosin uses ATP to generate force, the ATP pool needs to be continually replenished. During times of ischemia, the creatine phosphate pool, which converts ADP to ATP, may decrease.

Question 21

___________- when cardiac muscle is completely deprived of O2 because of occlusion of a coronary vessel, contractions quickly cease (within 30 seconds).

Answer 21

Heart failure

This is not due to depletion of either ATP or creatine phosphate because these levels decline more slowly. Even after 10 minutes of stopped-flow ischemia (occlusion of coronary vessels), when creatine phosphate levels are near zero and only 20% of the ATP remains, reperfusion (return of blood flow) can restore these energy stores, as well as contractile ability. However, prolonging the stopped-flow ischemia for 20 minutes results in further drops in ATP, so that reperfusion has considerably less effect, with only limited restoration of ATP and creatine phosphate levels or contractile activity.

Question 22

Symptoms of heart failure:

Answer 22

fatigue, dyspnea (shortness of breath) and reduced exercise tolerance.

Question 23

Heart failure can be caused by different factors and some of them are:

Answer 23

High blood pressure.
Ventricular wall weakening.
Defects in cardiac valves.

Question 24

____________________ can be prevented by the downregulation of phospholamban proteins (PLN proteins), which usually inhibit the activity of SERCA and increase the force of contraction. I

Answer 24

dilated cardiomyopathy

Question 24

Cardiac muscle can show hypertrophy. Some types of cardiac muscle hypertrophy are ____________, while some others are ________________

Answer 24

beneficial, pathological

Exercise such as running can increase the size of the heart as a result of an increase of individual cardiac muscle cells. As a consequence, the cardiac performance improves (beneficial contractile effects). This is called physiological hypertrophy because it has beneficial effects on the functions of the organ.

Pathological hypertrophy due to chronic pressure overload:
1) Dilated hypertrophy- an increase of ventricular volume.
2) Concentric hypertrophy- causes a thickening of the left ventricular wall, due to the increased load.

-Both of these cardiac hypertrophies cause:
A decreased contractile response to β-adrenergic stimulation.
Dysregulation of [Ca2+] caused by abnormal activity.
Alteration in Phosphorylation status of L‐type calcium channels, phospholamban, SERCA, RYR.

Question 25

Hypertrophic gene expression in the heart:

Answer 25

intracellular concentration of Ca2+ activates calcineurin (Ca+2-calmodulin dependent protein), which can dephosphorylate the nuclear factor of activated T cells (NFAT). The activation of Calcineurin modifies the NFAT family present in the cytoplasm and allows the translocation of the transcription factor from the cytoplasm into the nucleus. This promotes hypertrophy. This nuclear transcription factor is composed of two subunits, one in the cytoplasm, and the other in the nucleus. The impaired β-adrenergic response of the cardiac muscle after chronic pressure overload involves a decrease in β-adrenergic receptors (internalization).

The activation of Calcineurin-protein kinase is also implicated in the activation of other transcription factors like myocyte enhancer factor-2 (Mef2) which promote the dissociation of an inhibitor called Histone Deacetylase (HDAC).
-Increased Ca2+ may decrease activation of the Ca2+‐dependent phosphatases (cardiac hypertrophy), so downregulating PLN helps inhibit calcium storage in SR.