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Physiology > 2.2 Excitable tissue: Muscle > Flashcards

2.2 Excitable tissue: Muscle Flashcards

1
Q

What are the three types of muscle?

A

Skeletal - cross-striated, generally voluntary
Cardiac - cross-striated, functionally syncytial, involuntary
Smooth - not cross-striated
- visceral (unitary) - functionally syncytial
- and multiunit - eye, not spontaneously active

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2
Q

Discuss Skeletal muscle structure

What are characteristics of a muscle fiber?

A

made up of individual muscle fibres, most of which begin + end in tendons, arranged in parallel between tendinous ends so contractile force is additive.
NO syncytial bridges between cells in SkM

Each muscle fiber = single cell, multinucleated, long, surrounded by “sarcolemma” (cell membrane)
Muscle fiber is made up of “myofibrils” which are each made up of “myofilaments” with contractile proteins.

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3
Q

What are the key contractile proteins in skeletal muscle?

A

myosin-II
actin
tropomyosin
troponin (2 subunits, TnI, TnT, TnC)

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4
Q

What are striations?

A

See diagram in notes page 21 / Ganong 99
Cross-striations of skeletal muscle as seen under microscope, occur due to orderly arrangement of contractile proteins.
Z-lines allow for anchoring of thin filaments
Sarcomere = space between 2 adjacent Zs

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5
Q

What are the thick and thin filaments?

A

Thick filaments - Myosin-II
Has 2 heads containing an actin-binding site + ATP hydrolysis catalytic site.

Thin filaments
Actin - 2 chains of actin, forms a double helix
Tropomyosin - in the length of groove between the actin chains
Troponin - TnT binds tropomyosin, TnI inhibits interaction between myosin + actin, TnC has Ca2+ binding site to initiate contraction.

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6
Q

What are three additional structural proteins important to skeletal muscle function?

A

Actinin - binds actin to Z-lines
Titin - connects Z-lines to M-lines to scaffold the sarcomere, elastic domains
Desmin - binds Z-lines to cell membrane

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7
Q

Explain the sarcotubular system

A

The sarcotubular system is a system of membranous structures which surround the myofibrils
- Allows action potential to reach all myofibrils (even those located deeper) in the muscle fiber for coordinated contraction.
- Consists of T-system of transverse-tubules, which are continuous with the sarcolemma of muscle fiber, + the SR, which forms an irregular curtain around each myofibril.
- SR has enlarged “terminal cisterns” in close contact with T system at junctions between A+I bands.
“triads” - arrangement of central T-tubule with cistern of SR on either side.

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8
Q

What is the RMP of skeletal muscle?

A
  • 90mV
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9
Q

What is a muscle twitch?

A

A muscle twitch is the brief contraction + relaxation caused by a single action potential.
It begins ~ 2ms after start of membrane depolarisation.
Duration of twitch varies depending on type of muscle fibers - “fast-twitch” as short as 7.5ms, “slow-twitch” up to 100ms.

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10
Q

Describe/illustrate excitation-contraction coupling in skeletal muscle.

A

See notes page 21 / Ganong 103.

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11
Q

What is the SERCA pump?

A

Sarcoplasmic + endoplasmic reticulum Calcium ATPase - hydrolyses ATP to actively transport Ca2+ back into SR to facilitate muscle relaxation.

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12
Q

What is the mechanism of skeletal muscle contraction?

A

Sliding of thin filaments over thick filaments -
AP causes rise in cytosolic Ca2+
Ca2+ binds to TnC, releasing TnI to expose actin binding site for myosin head
Myosin-actin cross-bridge formation
Myosin releases ADP, undergoes conformational change of myosin head that moves thin filament relative to thick filament = “power-stroke”.
ATP binds to free site on myosin, causes detachment of myosin from actin.
ATP is hydrolysed, causes re-cocking of myosin head

Cycle ready to be repeated.

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13
Q

What is isometric vs isotonic contraction?

A

isometric - contraction without change in muscle length (possible because of elastic + viscous elements also contained in addition to contractile proteins)
isotonic - contraction with change in muscle length against a constant load, may be concentric (shortening) or eccentric (lengthening) - does work (positive + negative work)

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14
Q

Explain summation of contractions

A

Electrical response of muscle fibre is similar to a neuron, in that there is a refractory period.
However the contractile mechanism does not have a refractory period, so repeated electrical stimulation results in an additive response = “summation of contractions”
Fusion into one continuous contraction = “tetanic contraction”.
“Complete tetanus” - no relaxation between stimuli - the tension developed is 4x that of single twitch contractions.
“Incomplete tetanus” - period of incomplete relaxation between summated stimuli.
Required stimulation frequency for tetanus depends on twitch duration of particular muscle

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15
Q

What are the types of skeletal muscle fibres and their properties?

A 
Type - 
I - slow-oxidative
IIA - fast-oxidative-glyclolytic
IIB - fast-glycolytic
See notes 22 / Ganong 106 for properties
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16
Q

What is phosphorylcreatine?

A
  • Phosphorylcreatine - hydrolysed to creatine + phosphate groups with release of considerable energy.
    At rest, mitochondrial ATP transfers its phosphate to creatine to build up a phosphorylcreatine store - during exercise, this can then be used to form ATP and permit contraction to continue.
17
Q

Discuss metabolism of carbohydrates and lipids in muscle

A

Rest and during light exercise - muscles use lipids in form of FFAs as energy source

Increased intensity, lipids cannot supply energy fast enough -> carbohydrate is predominant energy source
Glucose -> CO2 + H2O
How? Glucose (and glycogen) are broken down into pyruvate. Pyruvate enters TCA cycle and is metabolised to CO2 and H2O via AEROBIC GLYCOLYSIS

If insufficient O2 (cannot use TCA cycle), pyruvate is reduced to lactate - ANAEROBIC GLYCOLYSIS (lower energy yield) - short term, self-limiting as lactate accumulation eventually exceeds buffering capacity, causing enzyme-inhibiting decline in pH.

18
Q

What is the oxygen debt mechanism?

A

Increased blood flow to exercising muscles delivers increased O2 supply.
To a point, increase in O2 consumption is proportional to energy expended + energy needs are met by aerobic metabolism.
When exertion is very great (utilisation of energy stores > aerobic resynthesis) -
1) Phosphorylcreatine is still used to resynthesise ATP, and
2) Anaerobic metabolism of pyruvate to lactate

E.g. 100m sprint - 85% anaerobic, vs long-distance/steady-state 5% anaerobic

After exertion, extra O2 is consumed to remove excess lactate, replenish ATP + phosphorylcreatine stores + replace myoglobin O2
= the OXYGEN DEBT, which is the proportional to extent to which energy demands exceeded capacity of aerobic metabolism.

19
Q

What are the types of heat production in skeletal muscle?

A

Resting heat - given off at rest, external manifestation of basal metabolic processes
Initial heat - heat produced in excess of resting heat, during contraction (made up of activation heat - due to contraction, and shortening heat, proportional to distance muscle shortens)
Relaxation heat - due to lengthening of muscle after isotonic contraction
Recovery heat - in excess of resting heat after contraction - heat liberated by restorative metabolic processes

20
Q

What is the motor unit? Do sizes vary? What about muscle fibre types? What is the association between size + type?
What is the size principle?

A
  • Motor unit = a single motor neuron + the muscle fibres it innervates
  • Size varies - e.g. hand, eye - fine, graded, precise - 3-6 muscle fibres / neutron
    vs leg - 600 fibres / neutron
  • All muscle fibres in a unit are of ONE type (i.e. duration of twitch contraction) - this defines types of motor units as S, FR, FF.
  • S fibres tend to be small units (low innervation ratio), FF are larger units.
  • smaller, S units are recruited first, then FR, then FF for most demanding tasks
21
Q

Discuss cardiac muscle morphology

A
  • Striations with Z-lines, similar to skeletal muscle. T-system is at Z-lines though, not A-I junction
  • Muscle fibres branch + interdigitate, each is complete unit surrounded by cell membrane.
  • One muscle fibre joins the next at “intercalated disks”, both membranes parallel each other in a series of folds - at Z lines - maintains cell to cell cohesion for uniform contractility
  • Next to intercalated disks are “gap junctions” for spread of excitation - allow function as a syncytium
22
Q

What is the RMP of cardiomyocytes?

A

-80 mV

23
Q

Draw typical ventricular cardiomyocyte action potential

A

See notes page 23 / Ganong 112

24
Q

How are myosin isoforms distributed in the heart?

A

alpha and beta myosin isoforms
alpha predominating in atria
beta in ventricles
spatial expression contributes to well-coordinated contraction of heart

25
Q

Explain Starling’s Law of the heart

A

The stroke volume (and thus developed ventricular tension) increases proportionally to the end diastolic volume in the ventricle

  • similar to in skeletal muscle, there is a “resting length” at which the tension developed by the muscle is maximal.
  • the length of the fibres is determined by EDV
  • the developed tension, increases as EDV increases until it reaches a maximum, then decreases.
26
Q

What factors increase cardiac contractility?

What factors decrease contractility?

A 
Increase - 
SNS
inotropes
digitalis
catecholamines
post extra-systolic potentiation
increase in HR (minimal)

Decrease -
PSNS
Intrinsic depression (MI, HF, cardiomyopathy)
Drugs (CCB, B-blocker, procainamide + barbiturates
hypoxia
hypercarbia
acidosis

27
Q

Discuss cardiac muscle metabolism

A
  • well established for aerobic metabolism, abundant blood supply + mitochondria, myoglobin for O2 storage
  • normally <1% of energy anaerobic, can increase to 10%
  • Basal energy sources: 35% carbohydrate, 5% ketones, 60% fat, varies with nutritional state
  • Circulating FFAs account for 50% of lipids used
28
Q

Discuss smooth muscle morphology

A
  • Different to skeletal + cardiac - lacks cross-striations
  • Actin + myosin-II still slide on each other to produce contraction, but not arranged in regular arrays.
  • “dense bodies” in cytoplasm + attached to cell membrane, instead of Z lines, bound by actinin to actin
  • has tropomyosin, but NOT troponin
  • SR is less extensive
  • few mitochondria, depend largely on glycolysis
29
Q

What are the two main types of smooth muscle?

A

Unitary (visceral) smooth muscle -
- large sheets, lots of gap junctions, syncytial function
- walls of hollow viscera
Multiunit smooth muscle -
- individual units with few or no gap junctions - in iris where fine, graded contractions occur.
- involuntary
both respond to hormones + circulating substances
blood vessels have both in their walls

30
Q

What is different about the resting electrical/mechanical activity of unitary smooth muscle?

A
  • unstable membrane potential, no true “resting” value - low when tissue active and high when inhibited, at “rest” fluctuates between -20 to -65mV
  • maintained state of partial contraction “tone”
  • slow sine wave-like fluctuations + occasional spikes
31
Q

How is contraction different in smooth muscle?

A
  • Ca2+ still plays an important role, but comes from many sources e.g. voltage or ligand-gated channels, RyR SR efflux, IP3R-activated effux, often combination
  • lack of troponin - instead, myosin is phosphorylated for activation of myosin ATPase
  • Ca2+ binds to CALMODULIN, and activates Calmodulin-dependent myosin light chain kinase - which phosphorylates myosin to increase its ATPase activity
    (dephosphorylation is by myosin light chain phosphatase)
32
Q

Give two examples of smooth muscle relaxants

A

B-agonists - airways, relaxation

NO - blood vessels, relaxation (down-regulated by PDE - PDE V inhibitors used to relax SM in corpus cavernosum)

33
Q

Discuss smooth muscle innervation + sensitivity to chemical agents

A
  • unitary smooth muscle usually has dual nerve supply from SNS + PSNS
  • SM has spontaneous activity in absence of nervous stimulation
  • function of nerve supply is not to initiate, but to MODIFY activity
  • in some organs, noradrenergic stimulation stimulation increases activity / cholinergic stimulation decreases activity - in others the reverse

Physiology (9 decks)

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