Excitable tissues: Muscle Flashcards
features of skeletal muscle (4)
- Under voluntary controla
- Striated
- Single long cylindrical cells
- Multiple peripheral nuclei
features of cardiac muscle (5)
• Located only in the heart • Striated • Branched cells with 1-3 central nuclei • Connected via intercalated discs • Involuntary control
Features of smooth muscle (4)
• Involuntary • Found in the wall of internal organs (gut, blood vessels etc) • Spindle shaped, uninucleated cells • Not striated
structure of skeletal muscle (3)
Attached to bones via tendons • The cells “muscle fibres” are long (up to 35 cm) and reasonably wide (0.1 mm) • Cells are composed of fibrils containing highly organised contractile filaments
Microscopic structure of a myofibril
Thick filaments: run the entire length of an A band
• Thin filaments: run the length of the I band and partway into the A band
• Z disc: coin-shaped sheet of proteins that anchors the thin filaments and connects myofibrils to one another
• H zone: lighter mid region where filaments do not overlap
• M line: line of protein myomesin that holds adjacent thick filaments
together
What are T tubules?
deep invaginations
continuous with the sarcolemma (cell membrane) and circle each
sarcomere at each of the junctions of the A and I bands. Allows action potentials to be carried deep within the muscle cell
what are Sarcoplasma reticulum (SR)?
The calcium storage site. The terminal cisternae of the SR lie close to the T-tubules.
What are the thick filaments? (3)
- Composed of Myosin
- Each myosin has 2 subunits each with a globular head and a tail, the two tails intertwine to form a helix
- The heads have a binding site for actin
what are thick myosin filament? (3)
• The head is an enzyme that hydrolyses ATP (an
ATPase)
• Arranged in a polarised fashion: i.e. with the myosin heads projection away from the M-line.
• Titin anchors the thick filament to the Z-line
What is the thin filament? (3)
• Composed primarily of globular actin proteins
• The filaments are composed of a double stranded helical actin chain (polymers).
• Troponin and tropomyosin are regulatory proteins
associated with actin in skeletal and cardiac muscle
What is troponin regulated by?
regulated by Ca2+
what does Tropomyosin interact with?
interact with the myosin-binding sites
Sliding filament theory of muscle contraction (3)
The sarcomere shortens as the thin filaments
are pulled over the thick filaments:
• The Z-line is pulled toward the M-line
• The I band and H zone become narrower
what are the 4 steps of the cross-bridge cycle (4)
- Cross-bridge formation
- Power stroke
- Detachment
- Energization of myosin head
Cross-bridge formation
Myosin binds to the actin-binding site to form a
cross-bridge
The Power Stroke (3)
• ADP is released
• The myosin head rotates to its low energy state
(about 45° to the actin) pulling with it the thin filament
• The result is a shortening of the sarcomere.
Detachment (2)
A new ATP molecule
binds to the myosin
The actin-myosin bind is
weakened and the
myosin detaches
Energization of the myosin head (2)
• Myosin head hydrolyzes the ATP to ADP + Pi
• The myosin head moves back to its “high energy
(cocked)” confirmation (about 90° to the actin)
what is the importance of calcium? (3)
• Calcium ions provide the “on”
switch for cross-bridge cycle to
begin.
• When the calcium binds with troponin the tropomyosin moves to expose the myosin-binding sites on actin
• The cross-bridge cycle will continue as long as calcium levels remain above the critical threshold (0.001-0.01 mM)
what happens in calcium regulation? (2)
• In skeletal muscle opening of calcium channels in the SR allows the movement of calcium ions into the
cytosol.
• Active transport pumps (Ca2+ATPase) are constantly
moving Ca2+ from the cytoplasm back into the sarcoplasmic reticulum
isotonic? (3)
Shortening
Tension constant
Velocity variable
Isometric? (3)
No shortening
Length constant
Tension variable
What is the Length-tension relationship? (2)
- During an isometric contraction –
- At the level of the sarcomere the maximum active force (tension developed) is dependent on the degree of actin and myosin overlap
Length-tension relationship (2)
• During an isometric contraction –
• At the level of the sarcomere the maximum active force (tension developed) is dependent on the
degree of actin and myosin overlap
what is Active tension? (3)
- At lengths <2.0 µm filaments collide and interfere with each other reducing force developed
- A lengths >2.2 µm active forces decline as the extent of overlap between filaments reduces, reducing the number of cross-bridges
- Maximal force between 2.0 – 2.2 µm
Why does total tension = active + passive force? (3)
- Of course muscle also has elastic components!
- As muscle is stretched the connective tissue around the muscle cells resists the stretch = passive force. •Total tension is the sum of the active tension dependent on the sarcomere length and the passive tension Total tension = active
What is Motor-unit?
A motor unit consists of a motor neuron and all the muscle fibers it innervates.
What is involved when ACh is released into neuromuscular junction? (3)
- An action potential travels down the motor neuron •At the axon terminal Ca2+ channels open, and Ca2+ enters the axon terminal
- This triggers the vesicles containing ACh to fuse with the terminal membrane, releasing ACh into the neuromuscular junction (synaptic cleft)
What is involved with the Activation of ACh receptors? (2)
•The binding of ACh to the receptors on the muscle end plate causes the opening of the ligand (ACh) gated ion channels. •Opening of these channels allows movement of predominantly Na+ into the muscle cell making it less negative (end plate potential)
What happens when a Muscle Action Potential is triggered? (3)
- If sufficient ligand-gated channels are opened the endplate potential reaches a threshold
- Voltage-gated Na+ channels open and an action potential is triggered
- The action potential is then propagated along the sarcolemma into the T tubule system
What happens when calcium is released from the SR? (3)
- The action potential is conducted down the t-tubules coming in close contact with the sarcoplasmic reticulum.
- This results in voltage-gated Ca2+ channels in the sarcoplasmic reticulum opening.
- Ca2+ is then released into the cytosol
What happens when Ca2+ binds with troponin?
When Ca2+ concentrations reach a critical threshold the myosin binding sites on the actin filament are exposed allowing the cross-bridge cycle to occur
How does contraction end when Ca2+ levels fall? (2)
- Calcium is actively pumped back into the sarcoplasmic reticulum via Ca2+-ATPase pumps
- Troponin moves back covering the myosin binding site
What is Muscle metabolism: Creatine Phosphate? (3)
For brief periods (<15s) creatine phosphate can act as an ATP “store”
• Creatine phosphate + ADP = creatine + ATP
• Anaerobic
What is anaerobic glycolysis? (3)
• Good for short intense exercise: fast but inefficient • Dominant system from about 10-30s of maximal effort • Build up of lactate and H+ limits duration to max 120s
what is aerobic metabolism? (4)
- Efficient, but comparatively slow.
- Requires oxygen, therefore good blood supply
- Max 300 W.
- Important for postural muscles and endurance exercise
What is type 1 (slow twitch)?
Units with neurons innervating the slow efficient aerobic cells (maintaining posture, walking)
What is type 2 (fast-twitch)?
Units with the neurons innervating the large fibers that fatigue rapidly but develop large forces (jumping, weight lifting)
What is the regulation of force dependant on? (2)
Dependent on:
• Rate of stimulation of individual motor units
• The number of motor units recruited
What happens when a single stimulus is delivered?
The muscle contracts and relaxes
what happens If another stimulus is applied before the muscle relaxes completely?
more tension results. This is temporal (or wave) summation and results in unfused (or incomplete) tetanus.
What happens at higher stimulus frequencies?
There is no relaxation at all between stimuli. This is fused (complete) tetanus
Intercalated discs? (3)
- Desmosomes prevent cells from separating during contraction
- Contain gap junctions that allow the action potentials to be carried from one cell to the next
- Allows for the co-ordinated contraction of all the myocytes (unlike skeletal muscle where fibres are recruited via the motor nerves)
What are the three major stages of an action potential in a cardiac muscle cell?
0 – Rapid depolarisation due to fast voltagegated Na+ channel
2 – Plateau phase due to slow voltage gated Ca2+ channel (L-type Ca2+ channel)
3 – Repolaristation due to closing of Ca2+ channels and opening of K+ (outward) channels
- Cardiac Muscle: excitation-contraction coupling (3)
- Depolarization opens voltage-gated fast Na+ channels in the sarcolemma. Reversal of membrane potential from –90 mV to +30 mV
- Depolarization wave opens slow (L-type) Ca2+ channels in the sarcolemma (DHPR)
- Ca2+ influx balanced by a Na+/Ca2+ exchanger
- Cardiac Muscle: excitation-contraction coupling (2)
- Ca2+ influx triggers the opening of Ca2+-sensitive channels in the SR (RyRa), which liberates bursts of Ca2+ (i.e. calcium-induced calcium release)
- The raised intracellular Ca2+ concentration allows Ca2+ to bind to troponin, which then switches on the contractile machinery
What needs to happen for relaxation to occur? (6)
For relaxation to occur [Ca2+] must decline, allowing Ca2+ to dissociate from troponin.
This requires Ca2+ transport out of the cytosol by four pathways (in green): • SR Ca2+-ATPase • sarcolemmal Na+/Ca2+ exchange • sarcolemmal Ca2+-ATPase • mitochondrial Ca2+ uniport.
Regulation of Cardiac Output (CO) equation
CO = SV x HR
what is heart rate set by?
Heart Rate (HR) is set by the pacemaker cells in the sinoatrial node. The rate can then be modified, especially via the autonomic nerves releasing neurotransmitters.
Autonomic innervation of the heart (2)
- Sympathetic cardiac nerves increase heart rate
and force of contraction (release noradrenaline) - The vagus nerve (parasympathetic) decreases heart rate. Release ACh
Neural control of heart rate (3)
Via alteration of pacemaker potential
Vagal nerves release acetylcholine (ACh): Decrease rate of spontaneous depolarization and hyperpolarises the resting membrane potential = decrease heart rate
Sympathetic nerves release
noradrenaline (NA): Increases rate of
spontaneous depolarization = increase
heart rate
What does stroke volume (SV) reflect? (4)
Stroke volume (SV) reflects the tension developed by the cardiac muscle fibres in one contraction. Can be increased by:
• increased rate of firing (heart rate/HR)
• increased stretch of ventricles (length)
• certain neurotransmitters (e.g. Noradrenaline)
What is automaticity?
Increasing heart rate increases contractile force (stroke volume)
- due to less time available for Ca2+ to be pumped out of the cell
Length tension relationship for cardiac muscle (3)
• Increased stretch (filling=preload) results in more force developed (stroke volume) • Starlings law of the heart: “as the resting ventricular volume is increased the force of the contraction is increased” • entirely intrinsic!
Neural control of stroke volume (4)
Noradrenaline (NE = NA) acting on β receptors and via second messengers acts on:
• L-Type channels resulting in more calcium entering the cell.
• Ca2+ pump in SR so SR increases its Ca2+ stores
Net result = bigger/shorter contraction
What does noradrenaline released by sympathetic
nerves lead to? This is due to? (4)
increased cytosol calcium due to increased HR shortening time for extrusion
And via second messengers (previous slide) :
- by increasing Ca++ influx (via Ca++ channels) during
the action potential (primarily during phase 2),
- by increasing the release of Ca++ by the sarcoplasmic reticulum (due to greater SR uptake)
What does increased sympathetic stimulation result in?
Increased sympathetic stimulation results in increased output at any filling pressure due to increase in inotropy and heart rate
Basic structure single unit?
sheets of cells that are electrically coupled and act in unison i.e. as one unit - often spontaneously active.
Found in most blood vessels and hollow organs (respiratory, digestive, urinary and reproductive tracts)
Basic structure multiunit?
tissue made of discrete bundles of independent cells which are densely innervated and contract only in
response to its innervation (e.g., vas deferens, iris, piloerectors)
Arrangement of smooth muscle in the walls of hollow organs “Unitary” smooth muscle. (3)
Longitudinal layer of smooth muscle (shows
smooth muscle fibers in cross section)
Circular layer of smooth muscle (shows longitudinal
views of smooth muscle fibers)
Cross section of the intestine showing the
smooth muscle layers (one circular and the other
longitudinal) running at right angles to each other.
Basic cellular structure (5)
- No T-tubules – caveolae instead (act to increase surface area)
- Dense bodies act like z-lines to “anchor” actin to sarcolemma
- In unitary smooth muscle cells gap junctions electrically connect the cells together
- Intermediate filament is cytoskeleton element
- Poorly developed SR
Contractile proteins (2)
No striations, but contains actin and myosin filaments
Less organized – actually allows for greater shortening: Can operate over large range of lengths (60 - 75% shortening possible)
Initiation of contraction
Electrical behaviour very complex but primarily due to voltage-gated Ca2+ channels (relatively few Na+ channels)
Trigger for contraction is an increase in intracellular calcium. The Ca2+ entering through channels in the cell membrane is a very important source of calcium (i.e. less reliant on SR stores)
Calcium regulation in smooth muscle
Calcium source: Extracellular and SR Regulation via voltage, hormones, neurotransmitters and specific ions
Initiation of contraction
- Calcium ions (Ca2+) enter the cytosol from the ECF via voltage-dependent or voltage-independent Ca2+ channels, or from the scant SR
- Ca2+ binds to and activates calmodulin
- The activated calmodulin then activates myosin light chain kinase (MLCK). MLCK is an enzyme.
- MLCK activates the myosin by phosphorylating it, which in turn activates the myosin ATPases.
- Activated myosin forms cross bridges with actin of
the thin filaments and shortening begins in the usual
fashion
