Nerves and Muscles 5

Question 1

What are the three types of muscle? What are their features?

Answer 1

Smooth muscle:

• Non-branched
• Some are auto-rhythmic - any innervation is received from hormones or the ANS.
• Non-striated
• Lines hollow organs, blood vessels, eyes, glands etc.

Cardiac muscle:

• Branched
• Auto-rhythmic
• Striated
• Makes up the myocardium
• Rich in myoglobin, glycogen and mitochondria
• Interconnected

Skeletal muscle:

• Non-branched
• Requires somatic nervous stimulation. It is voluntary.
• Striated
• Attached to the skeleton
• Makes up 40% of body weight

Question 2

What are intercalated discs? What are they composed of?

Answer 2

Intercalated discs are the specialised overlap between the muscle cells.

Made up of:

• Fascia Adherens - Anchoring sites of actin and so connect the adjacent sarcomeres.
• Desmosomes - Stop separation of sarcomeres duding contraction by binding intermediate filaments.
• Gap junctions - enable the flow of ions from one cell to another and therefore enable the spread of the action potential.

Question 3

What percentage of the skeletal muscles and cardiac muscle is made up of mitochondria?

Answer 3

Skeletal muscle: 2%

Cardiac muscle: 30%

Question 4

What features of cardiac muscles are due to gap junctions?

Answer 4

• Auto-rhythmic cells can cause the fibres around the cell to contract
• The cardiac muscle of the atria and of the ventricles behave as a single unit - Functional syncithium
• Transmission is bidirectional
• Under the control of the ANS and endocrine

Question 5

What is the difference between contractile cells and auto-rhythmic cells?

Answer 5

Contractile cells:

• Do not initiate action potentials
• Have a resting potential
• Contract the heart

Auto-rhythmic cells:

• Can initiate action potentials
• Do not have a resting potential - the membrane of these cells are leaky and so neural input is not necessary to initiate an AP.
• Slow depolarisation which drifts towards threshold

Question 6

Why are myocytes in coronary schema described as irritable?

Answer 6

Depolarisation of one irritable myocyte rapidly propagates via the all-or-nothing principle which can lead to arrhythmia.

Question 7

What is difference in refractory period between skeletal muscle, contractile myocardium and auto-rhythmic myocardium?

Answer 7

Skeletal muscle: generally brief

Contractile period: Long because resetting of Na+ channel gates delayed until end of action potential.

Auto-rhythmic myocardium: None

Question 8

Why is resting heart rate lower than the heart rate driven by the SAN?

Answer 8

Due to vagal tone

Question 9

How is a heart beat initiated?

Answer 9

1. The SAN node initiates a wave of depolarisation across the aria causing the atria to contract.
2. There is a layer of fibrous tissue and so the wave does not transmits directly to the ventricles. The wave the meets the AVN.
3. The AVN transmits the wave does to the Bundle of His which takes the impulse down to the apex and up the ventricles.
4. The wave of depolarisation travels across to cause the ventricles to contract via the Purkinje fibres.

Question 10

What is Wolff-Parkinson-White Syndrome (WPW)?

Answer 10

The wave of depolarisation travels down an alternative route called the Bundle of Kent. This causes the ventricles to contract prematurely resulting in supra ventricular tachycardia.

Question 11

What is the rate of activity of the SAN?

Answer 11

90-100 bpm

Question 12

What is the rate of activity of the AVN?

Answer 12

50-70 bpm

Question 13

What is the area of activity of the Bundle of HIs?

Answer 13

20 - 40 bpm

Question 14

What is sick sinus syndrome?

Answer 14

When the SAN become fibrous and loses its ability to spontaneously depolarise. These symptoms have bradycardia and symptoms of hypertension.

Question 15

What are the different phases of ventricular action potential?

Answer 15

Phase 0: Lag phase - the membrane potential is constant. This enables time for the Na+ channels to open.

Phase 1: Depolarisation. Sodium ion channels are open and so sodium enters the cell depolarising the membrane. Eventually permeability stops and sodium channels close.

Phase 2: The plateau region due to influx of calcium ions due to slow channels and also inward movement of
sodium through channel and decrease in membrane K+ conduction.

Phase 3: Membrane potential closes exponentially as potassium ion channels open and potassium leads the cell. There is decreased permeability to calcium.

Phase 4: The potential is static, it does not drift now at resting potential.

Question 16

What are Class I anti-arrhythmic drugs?

Answer 16

Sodium ion channel blockers. Used in the treatment of ventricular ectopics.

Question 17

What are Class II anti-arrhythmic drugs?

Answer 17

Beta blockers. Used to slow conduction in the SAN and AVN. They act by blocking the effects of catecholamines at the β1-adrenergic receptors, thereby decreasing sympathetic activity on the heart. These agents are particularly useful in the treatment of supraventricular tachycardias. They decrease conduction through the AV node.

Question 18

What are Class III anti-arrhythmic drugs?

Answer 18

Potassium ion channel blockers. They prolong hyper polarisation. Treat ventricular tachycardia and atrial fibrillation.

Question 19

What are Class IV anti-arrhythmic drugs?

Answer 19

Calcium ion channel blockers. Used to slow conduction in the SAN and AVN.

Question 20

What is the difference between skeletal muscle action potential and cardiac muscle action potential?

Answer 20

Skeletal muscle have a short refractory period (10 - 100ms) and twitch for a long time. They also allow for tetanus. Cardiac muscle has a long (250 ms) refractory period which is as long as muscle twitch. As a result summation cannot occur. During the relaxation phase. The atria fill up with blood and so does the ventricles. Without the relaxation, the heart cannot fill up with blood. The heart muscle relax so that when it relaxes again, it can eject the blood. The heart will not undergo tetanus.

Question 21

How is excitation and contraction coupled in cardiac muscle?

Answer 21

The action potential enters from the adjacent cell through T-tubules which are in close proximity to the sarcoplasmic reticulum. The entry of the action potential causes L-type voltage-gated calcium channels to open and Ca2+ to enter. the entry of calcium ions triggers the release of more calcium from the sarcoplasmic reticulum. This is known as calcium induced - calcium release. Calcium then binds to to troponin to initiate contraction.

Question 22

How does Noradrenaline have an effect on cardiac muscle?

Answer 22

Noradrenaline increases the contractile force of the heart. It acts through the beta-type adrenergic receptor to increase cAMP, to activate PKA which phosphorylates the L-type channel, increasing passive Ca2+ influx.

Question 23

How does relaxation of the cardiac muscle occur?

Answer 23

Calcium unbinds and is taken up by the sarcoplasmic reticulum by an active process. The rest fo the calcium is co-exchanged with sodium. The sodium gradient is marinated by these sodium-potassium ATPase.

Question 24

How does Digoxin work?

Answer 24

Digoxin acts by inhibiting the sodium-potassium ATPase pump. This means that the sodium concentration cannot increase. The sodium-calcium pump usually causes 3 sodium ions to enter the cell for every 1 calcium ion left. This increased sodium concentration causes the pump to reverse and so they calcium concentration available to contractile proteins remain high. This increases the force of contraction. Increased intracellular calcium causes an increase in the refractory period and so a decreased heart rate.

Question 25

What are the membrane potentials at the SAN for the following:

(i) Resting potential
(ii) Threshold

Answer 25

(i) - 60 mV

(ii) -40 mV

Question 26

Describe the stages of SAN depolarisation.

Answer 26

Pacemaker potential
There is gradual depolarization from -60 mV, due to slow influx of Ca2+, and reduced K+ permeability.

Action potential occurs at threshold of -40 mV
Depolarizing phase to 0 mV
Due to fast Ca2+ channels open, (Ca2+ in)
Repolarizing phase
K+ channels open, (K+ out)
at -60 mV, K+ channels close, pacemaker potential starts over
Each depolarization creates one heartbeat

Note resting membrane potential is not stable due to slow influx of Ca2+. At threshold Ca2+ channels open and rapid depolarization - cardiac action potential.
Repolarization - Ca2+ channels close and K+ open until membrane potential reaches -60 mV – then repeats.

Question 27

What is the Frank-Starling Law of the heart?

Answer 27

Cardiac output increases or decreases in response to changes in heart rate or stroke volume. The resting length of cardiac muscle cells is set below its ‘optimal level’ (i.e. when the heart is in diastole, the degree of overlap between the thick and thin filaments in the ventricular muscle cells is less than optimal). This means that, up to a point, stretching the cells more will result in a greater degree of myosin–actin overlap and, therefore, in an increase in the amount of force generated when the cells contract.

Question 28

What is the structure of smooth muscle?

Answer 28

Smooth muscle is made up of 2 layer: it is made up of an inner circular layer and an outer longitudinal layer.

• It has no clear sarcomere. The thick and thin filaments are not well organised.
• There are no T-tubules and the sarcoplasmic reticulum is poorly developed - instead there are Caveolae which are indentations in the sarcolemma which may act like T-tubules
• They are spindle shaped, with a single central nucleus
• The myosin to actin ratio is very high, 16:1 compared to 2:1 in skeletal muscle
• The fibres are small (2-10 microns in width and 40-600 microns in length)
• Spindle shaped

Question 29

What does calcium bind to in smooth muscle?

Answer 29

Calmodulin

Question 30

How does smooth muscle contract and relax?

Answer 30

1. Calcium binds to calmodulin. This interacts with myosin kinase to phosphorylate myosin.
2. Once phosphorylated, this generates tension isn a similar way as that in skeletal muscle.
3. The cytoplasmic calcium concentration falls, and so the calcium-calmodulin complex dissociates inactivating myosin kinase.
4. The cross bridges are de-phosphorylated by myosin phosphatase.

Question 31

Why is ATP consumption reduced in smooth muscle?

Answer 31

Smooth muscle has a slow ATPase rate so once attached, it takes a long time for each cross bridges to detach from the actin filament. The rate of calcium ion removal from the cytoplasm is low and so prolonging the duration fo contraction.

This means cross-bridging cycling is slower and so smooth muscle contraction occurs more slowly and the duration of the contraction with response to a stimulus is long. As a result smooth muscle can be used in sphincters to maintain force for long periods of time.

Question 32

What is the difference between single and multi unit smooth muscle?

Answer 32

Single-unit smooth muscle produces slow, steady contractions that allow substances, such as food in the digestive tract, to move through the body. Multi-unit smooth muscle, the second type of smooth muscle observed, are composed of cells that rarely possess gap junctions, and thus are not electrically coupled.

In single-unit muscles there are gap junctions and so the fibres can act as one unit. Electrical activity may arise spontaneously due to the presence fo pacemaker cells. Action potentials are developed in such cells. Nervous regulation is by the ANS. They contract in response to stretch - a myogenic response. In multi-unit smooth muscles, the cells lack gap junctions and cells are innervated individually.

In multi-unit smooth muscle, the innervation is automatic. There is no inherent response to stretch., The contractions are slow and sustained. This allows for fine controls such as in Hillary muscles of the eye controlling the size of the pupil and piloerector muscles of hair follicles.

Question 33

What is special about the post synaptic structure in smooth muscle?

Answer 33

It is not present.

Question 34

What is the cause of ending potential in the 3 types of muscle?

Answer 34

Cardiac muscle: Repolarisation of action potential

Skeletal muscle: The removal of neurotransmitters

Smooth muscle: The de-phosphorylation of myosin by myosin phosphatase.

Question 35

How is the control of force developed in the 3 types of muscle?

Answer 35

Cardiac muscle: Regulation of calcium activity

Skeletal muscle: Spatial and temporal summation

Smooth muscle: Latch bridge state - All the molecular force-generating states of de-phosphorylated, slowly detaching cross-bridges.

Question 36

What is the stimulus for excitation in the 3 muscle types?

Answer 36

Cardiac muscle: Pacemaker potentials and electrical coupling via gap junctions.

Skeletal muscle: Innervation at the neuromuscular junction

Smooth muscle: Many stimuli; this can include:

• Hormones
• Pacemakers
• Coupling via gap junctions

Question 37

What is dilated cardiomyopathy?

Answer 37

A condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. The muscle becomes weak, and inefficient. This causes fluid to build up in the lungs causing breathlessness and left heart failure.

Causes include:

• Viral infection
• Auto-immune disease
• Excessive alcohol consumption/exposure
• Pregnancy
• Familial disease

Question 38

What is hypertonic cardiomyopathy?

Answer 38

It is the thickening of muscle; may thicken in normal individuals as a result of high blood pressure or prolonged athletic training. This can happen due to no obvious cause. The normal alignment of the muscle cells is absent. It is well-known as a leading cause of sudden cardiac death in young adults. HCM is frequently asymptomatic until sudden cardiac death.

There is no obstruction to the outflow and there is no symptoms. The septum can show hypertrophy but this can lead to the whole of the heart becoming enlarged. This can lead to general heart symptoms - breathlessness, syncope etc. If extremely large, it can cause obstruction and lead to more severe symptoms.

Tend to be desomones that are altered so there isn’t the normal interaction of myocytes.

Question 39

What are leiomyoma?

Answer 39

Fibroids
They are begin growths in the smooth muscle of the female reproductive tract. There are usually multiple, varying in diameter. They are more prevalent approaching menopause and can lead to heavy uterine bleeding or pain. The cause is unknown but can be associated with factors such as genetics. The causes are unknown but it is suspected to be genetic. They are most common in people of afro-caribbean decent. High prevalence (60%) but not everyone has symptoms.