Cardiac and Smooth Muscle Flashcards
(80 cards)
1
Q
What is skeletal muscle controlled by?
A
Somatic motor neurones (voluntary)
2
Q
Describe cardiac muscle
A
- Striated (like skeletal), branched, interconnected
- Cardiac smaller than skeletal muscle cells
- Rich in glycogen, myoglobin and mitochondria
- Striated, with characteristic A and I-bands
- Contains actin & myosin myofilaments
3
Q
What is cardiac muscle controlled by?
A
Controlled involuntarily by endocrine and autonomic nervous systems
4
Q
Describe mitochondria of cardiac compared to skeletal
A
Mitochondria comprise 30% of volume of the cell vs. only 2% in skeletal
5
Q
What is function of intercalated discs in cardiac muscle?
A
Specialised cell-cell contacts as cell membranes interlock. 2 functions:
- Mechanical coupling –> Desmosomes hold cells together
- Electrical coupling –> Gap junctions allow action potentials to spread quickly to adjoining cells
6
Q
What are intercalated discs?
A
Intercalated discs are unique structural formations found between the myocardial cells of the heart. They play vital roles in bonding cardiac muscle cells together and in transmitting signals between cells
7
Q
What are the 3 types of cell junction that make up an intercalated disc?
A
- Fascia adherens
- Desmosomes
- Gap junctions
8
Q
What are fascia adherens?
A
- Anchoring sites for actin
* Connect to closest sarcomere
9
Q
What are desmosomes?
A
- Stop separation during contraction by binding intermediate filaments, joining the cells together
- Also known as macula adherens
10
Q
What are gap junctions?
A
Allow action potentials to spread between cardiac cells by permitting the passage of ions between cells, producing depolarisation of the heart muscle
11
Q
What cells are autorhytmic?
A
Fibres spontaneously contract (sino atrial node) - Pacemaker cells)
12
Q
What are arrythmias?
A
In the patient with coronary ischemia, areas of heart muscle can begin to randomly depolarise
Depolarisation of one irritable myocyte rapidly propagates via the all-or-none principle, which can lead to a fatal arrhythmia (ventricular fibrillation or ventricular tachycardia). Fatal arrhythmias are the most common cause of sudden death during a myocardial infarction.
13
Q
What are the 2 cell types in cardiac muscle?
A
- Contractile cells
2. Autorhythmic cells
14
Q
Describe contractile cells
A
• Myocytes contract the heart
- Don’t initiate their own AP
15
Q
Describe autorhythmic cells
A
- Initiate APs
- No stable resting membrane potential (Neural input not necessary to initiate an AP)
- Pacemaker activity instead ( Slow depolarization, drift to threshold, then firing)
16
Q
Describe membrane potential of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Stable at -70 mV
- Stable at -90 mV
- Unstable pacemaker potential (usually starts about -60 mV)
17
Q
Describe events leading to threshold potential of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Net Na+ entry through ACh operated channels
- Depolarisation enters via gap junctions
- Net Na+ entry through If channels, reinforced by Ca2+ entry
18
Q
Describe rising phase of AP of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Na+ entry
- Na+ entry
- Ca2+
19
Q
Describe repolarisation phase of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Rapid –> caused by K+ efflux
- Extended plateau caused by Ca2+ entry, rapid phase caused by K+ efflux
- Rapid, caused by K+ efflux
20
Q
Describe hyperpolarisation of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Due to excessive K+ efflux at K+ permeability when K+ channels close, leak of K+ and Na+ restores potential to resting state
- None (resting potential is -90mV, the equilibrium potential for K+)
- Normally none, when repolarisation hits -60mV, the If channels open again. ACh can hyperpolarise the cell
21
Q
Describe AP of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Short
- Extended
- Variable
22
Q
Describe refractory period of:
- Skeletal muscle
- Contractile myocardium
- Autorhythmic myocardium
A
- Generally brief
- Long because resetting of Na+ channel gates delayed until end of AP
- None
23
Q
How is pacemaker potential conducted from nodal tissue to adjacent contractile cells and beyond?
A
Through gap junctions in intercalated discs
24
Q
What is Wolff-Parkinson-White (WPW) Syndrome?
A
Disorder of the conduction system of the heart, referred to as pre-excitation syndrome
25
What is WPW syndrome caused by?
Caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles
26
What does WPW lead to?
Electrical signals travelling down this abnormal pathway (known as the bundle of Kent) may stimulate the ventricles to contract prematurely, resulting in a unique type of supraventricular tachycardia referred to as an atrioventricular reciprocating tachycardia.
27
What is complete heart block caused by?
• No transmission through the AV node
o His-Purkinje fibres take over pacemaker (pace the heart between 20 and 40 beats/min)
o Slower pacemaker activity in distal parts of the conducting system allows the heart to continue beating if the SA node fails
28
What is heart rate and cardiac output like of patients with complete heart block?
- Bradycardia
| - Reduced cardiac output
29
What are the 4 main classes of anti arrhythmic agents?
1. Class I --> Sodium channel blockers
2. Class II -- Beta blockers
3. Class III --> Potassium channel blockers
4. Class IV --> Calcium channel blockers
30
How do beta blockers work?
- Block effects of catecholamines at the B-1 adrenergic receptors
- Decreases sympathetic activity on heart
- Decrease conduction in SA and AV nodes
31
What are beta-blockers used to treat?
Treatment of supraventricular tachycardias
32
How do K+ channel blockers work?
Block potassium channels, thereby prolonging repolarisation
33
What are K+ channel blockers used to treat?
Treat ventricular tachycardia & atrial fibrillation
34
How do Ca2+ channel blockers work?
* Decrease conduction through AV & SA nodes
* Shorten phase II (plateau) of cardiac action potential
* Reduce contractility of the heart, not appropriate in heart failure
35
How do Ca2+ channel blockers contrast to beta-blockers?
They allow body to retain adrenergic control of heart rate and contractility
36
What is SA and AV node AP upstroke dependent on?
Ca2+ dependent
37
What is ventricular upstroke dependent on?
Na+ dependent
38
Skeletal muscle has a short refractory period but a longer twitch. After the refractory period the muscle can re-stimulated, what does this allow?
During the muscle contraction allows summation of twitches
39
How is cardiac muscle refractory period in relation to the twitch?
* Cardiac muscle long refractory period as long as the muscle twitch
* Can’t get summation
40
Describe cardiac excitation-excitation coupling
* Action potential invades the T-tubules (just as in skeletal muscle)
* This opens voltage-gated L-type Ca2+ channels in the T-tubule membrane (there is an abundance of these channels, unlike the situation in skeletal muscle)
* Ca2+ enters through L-type Ca2+ channels
* This triggers further Ca2+ release from adjacent sarcoplasmic reticulum (SR) as Ca2+ influx from L-type channel is not sufficient for contraction
* Amplifies Ca2+ (‘calcium induced calcium release’)
* Ca2+ binds to troponin-C
* Contraction proceeds in same way as in skeletal muscle
* The channels in the SR remain open after the L-type close
* Each L-type channel appears to control only one SR release channel due to the local structure, this means tight local control
41
Where does AP invade in cardiac muscles? What does this cause?
T-tubules
This opens voltage-gated L-type Ca2+ channels in the T tubule membrane (there is an abundance of these channels, unlike the situation in skeletal muscle) and Ca2+ enters
42
What does Ca2+ entering cardiac muscles result in?
This triggers further Ca2+ release from adjacent sarcoplasmic reticulum (SR)
Amplifies Ca2+ (‘calcium induced calcium release’)
43
Why is further Ca2+ released from adjacent SR?
As Ca2+ influx from L-type channel is not sufficient for contraction
44
What does Ca2+ bind to in cardiac cell?
Troponin-C
45
What occurs after Ca2+ binds to troponin-C?
* Contraction proceeds in same way as in skeletal muscle
| * The channels in the SR remain open after the L-type close
46
Why does each L-type channel appear to control only one SR release channel?
Due to the local structure, this means tight local control
47
How does noradrenaine affect the heart?
increases the contractile force of the heart
48
How does noradrenaline increase 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.
49
How does digitalis glycosides (e.g. digoxin) act to treat heart conditions?
Inhibits Na+/K+ ATPase pump (mainly in myocardium)
50
What does inhibition of Na+/K+ ATPase result in?
This causes an increase in intracellular Na+ levels which results in reversal of the action of the sodium-calcium exchanger which normally imports 3 intracellular Na+ ions into cell and 1 intracellular Ca2+ ion out of cell
51
What does reversal of this exchange (Na+/K+ ATPase) result in?
An increase in the intracellular calcium concentration that is available to the contractile proteins
52
What does increase in the intracellular calcium concentration result in?
- Lengthens phase 4 and phase 0 of the cardiac action potential which leads to a decrease in heart rate
- Increased storage of Ca in SR
53
What does increase in storage of Ca in SR lead to?
Causes corresponding increase in the release of calcium during each action potential
o This leads to increased contractility (force of contraction) of the heart without increasing heart energy expenditure
54
What is effect of ACh from parasympathetic nerves on pacemaker function?
o Stimulates vagus nerve
o Decrease SA node rate
o Decrease heart rate
55
What is effect of noradrenaline from sympathetic nerves on pacemaker function?
o Increases rate of depolarisation of pacemaker cells of SA node
o Develop action potentials at an increased rate
o Increase heart rate
56
The resting length of cardiac muscle cells is set below its 'optimal level'. What does this mean? What does this result in?
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
57
What are smooth muscles controlled by?
• Involuntary muscles
o Controlled by endocrine and autonomic nervous systems
o Usually 2 sheets of closely opposed fibres that overlay one another (one is circular and one is longitudinal)
58
What does alternating contraction and relaxation of 2 layers in smooth muscle cause?
Mixes substances in lumen of hollow organs (peristalsis)
59
What can excessive smooth muscle contraction in the respiratory tract cause?
Difficulty breathing --> asthma attack
60
What can inadequate tone in vascular smooth muscle cause?
Septic shock --> an overwhelming infection releases inflammatory mediators that cause dilation of systemic blood vessels, resulting in severe hypotension
61
Describe fibres of smooth muscle compared to skeletal muscle?
Smaller fibres, more actin than myosin (16:1, 2:1 in skeletal), no sarcomeres, no striation, no troponin, no T-tubules
62
What is contraction in smooth muscle regulated by?
By Ca2+ via a protein called calmodulin and an enzyme called myosin kinase
63
What does contraction of smooth muscle depend on?
Increase in cystolic Ca2+
64
What is contraction of smooth muscle regulated by?
Myosin molecules of the thick filament (not by the thin filament which lacks troponin, unlike skeletal and cardiac mscle)
65
What must occur before cross bridges can form in smooth muscle contraction?
Myosin molecule must be phosphorylated at a specific site on the myosin ‘light chains’
66
What does Ca2+ bind to in smooth muscle?
Calmodulin (not troponin) which interacts with enzyme myosin kinase to phosphorylate myosin
67
Once myosin cross bridge is phosphorylated by myosin kinase in smooth muscle, what happens?
It is capable of attaching to actin filament and generating tension in a similar way as occurs in skeletal muscle
68
What happens when cytoplasmic Ca2+ falls in smooth muscle?
The Ca2+-calmodulin complex dissociates, inactivating myosin kinase
69
What are the cross bridges in smooth muscle dephosphorylated by?
By the enzyme myosin phosphatase
70
What is an important feature of smooth muscle?
Its ability to maintain force over long periods of time (eg Sphincters)
71
Why does contraction of smooth muscle occur more slowly?
Cross bridge cycling is much slower
The duration of the contraction in response to a stimulus is long
Reduced ATP consumption
72
Why is cross bridge cycling in smooth muscle slower?
1. Smooth muscle myosin has a slow ATPase rate so once attached, it takes a long time for each cross bridge to detach from the actin filament
2. The rate of Ca2+removal from the cytoplasm is slow, so prolonging the duration of contraction
73
What is single-unit (unitary) smooth muscle?
• Most common
• Gap junctions so act as single unit
• Electrical activity may arise spontaneously due to the presence of ‘pacemaker’ cells
--> Action potentials are developed
• Nervous regulation is via the autonomic nervous system
74
What is multi-unit smooth muscle?
* Lack gap junction --> cells innervated individually
* Allows fine control, examples include ciliary muscle of the eye controlling size of pupil and piloerector muscles of hair follicles
* Not spontaneously active
* Innervation is autonomic
* There is no inherent response to stretch
* Contractions are slow and sustained
75
What are varicosities?
Autonomic nerves make multiple contacts with the cell
No specialised postjunctional membrane, receptors spread across cell membrane.
76
What is molecular basis for:
1. Cardiac muscle
2. Skeletal muscle
3. Smooth muscle
1. Ca2+-troponin C
2. Ca2+-troponin C
3. Ca2+-calmodulin
77
What causes the end of contraction of:
1. Cardiac muscle
2. Skeletal muscle
3. Smooth muscle
1. Repolarisation of AP
2. Breakdown of ACh in NMJ
3. Myosin light chain phosphatase activity
78
What is dilated cardiomyopathy?
* Heart enlarges, functions poorly
* Muscle becomes weak, inefficient causing fluid build-up in the lungs, → breathlessness → left heart failure
* Right heart failure → fluid build-up in tissues & organs (legs, ankles, liver, abdomen)
79
What is hypertrophic cardiomyopathy?
A disease of the myocardium in which a portion of the myocardium is hypertrophied (thickened) without any obvious cause
May thicken in normal individuals as a result of high blood pressure or prolonged athletic training
80
What is leiomyoma (fibroids)?
A smooth muscle disorder
* Benign growth
* Female reproductive tract
* Heavy uterine bleeding &/or pain
