Module 7 (ET muscle) Flashcards
Types of muscles
Skeletal, cardiac and smooth
Striated muscle
Skeletal and cardiac; highly ordered contractile system leading to a banded appearance with bands occurring with a periodicity of about 2um
Non-striated muscle
Smooth muscle
Voluntary muscles
Skeletal; responsible for the movement of limbs; attached to bones which act as levers to provide a greater range of movement
Involuntary muscles
Cardiac for pumping blood; smooth for lining blood vessels and hollow organs, responsible for altering their dimensions; may have intrinsic contractile activity whose amplitude and/or frequency is modulated by nervous system input (myogenic); others may be quiescent and their contraction initiated by autonomic nervous system input
Motor unit
A group of muscle cells which are innervated by a single motor neuron
Structure of skeletal muscle
Most highly ordered of muscles; attached to bones via tendons; the cells (muscle fibres) are up to 35cm long and 0.1cm wide; cells composed of fibrils which run the length of the cell and contain highly organised contractile filaments; SR surrounds the fibril and stores calcium, releases it to activate contraction
Fibrils in skeletal muscle
Run the length of the cell; made up of alternating bands of myosin and actin filaments which interdigitate
Sarcomere
Basic contractile element; consists of an array of thick and thin filaments, attached to Z-discs at each end; t-tubules invaginate the surface membrane of the cell (sarcolemma) and are surrounded by the SR
Thin actin filaments
Globular proteins that form thin filaments within the cell; may have accessory proteins attached to them which regulate their activity (such as troponin and tropomyosin)
Thick myosin filaments
High molecular weight protein that is formed from two high molecular weight sub-units which each have a tail that wind around each other in a double helix and a globular head able to hydrolysed ATP; accessory proteins regulate this ability
A-band
Thick filaments run the entire length; some thin filament
I-band
Thin filaments run length
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
T-tubules
Deep invaginations continuous with the sarolemma (cell membrane) and circle each sarcomere at each of the junctions of the A and I bands; allows APs to be carried deep within the cell
SR
Sarcoplasmic reticulum; calcium storage site; terminal cistenae lie close to the T-tubules
Sliding filament theory
Sarcomere shortens as the thin filaments are pulled over the thick filaments; Z-line pulled toward M-line; I band and H zone become narrower
Cross-bridge cycle
Cross-bridge formation; power stroke; detachment; energisation of myosin head
Cross-bridge formation
Myosin binds to the actin binding site to form a cross-bridge; can only occur in the presence of calcium when the myosin biding site on actin is exposed; the myosin head has already hydrolysed ATP so ATP needs to be available
The power stroke
ADP is released; myosin head rotates to its low-energy state (about 45degrees to the actin) pulling with it the thin filament; result is shortening of the sarcomere
Detatchment
A new ATP molecule bind to the myosin; the actin-myosin bond is weakened and the myosin detaches; if there is no ATP, rigor mortis (stiffness) will occur because there is no energy available and the myosin stays attached to the actin
Energisation of the myosin head
Myosin head hydrolyses the ATP to ADP and Pi; the myosin head moves back to its high energy (cocked) conformation about 90degrees to the actin
Importance of calcium
Calcium ions provide the on switch for the cross-bridge cycle to begin; when it binds with troponin, the tropomyosin moves to expose the myosin binding sites on actin; the cross-bridge cycle will continue as long as calcium remains above the threshold
Calcium regulation
In skeletal muscle, the 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 SR
Isotonic
Contraction where the tension developed in the muscle remains almost constant while the muscle changes length;shortening; tension constant; velocity variable
Isometric
Contraction where the tension developed does not exceed the resistance of the object and there is no change in muscle length; no shortening; length constant; tension variable
Length-tension relationship
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
Optimal resting length
The greatest tension produced due to maximum number of cross-bridges formed; 2.0-2.2.um
Sarcomere length decreases
Decrease in length reduces tension due to extensive overlap; no tension can form when thick filaments meet Z-lines and sarcomeres cannot shorten; <2.0um filaments collide and interfere
Sarcomere length increases
Reduced size of zone of overlap means fewer cross-bridges are formed and reduced tension; zero zone of overlap results in zero tension due to no interactions between thick and thin filaments; >2.2um active forces decline as the extent of overlap between filaments reduces
Total tension
Active + passive forces; 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 passive tension
Neuromuscular junction
Synaptic cleft; chemical synapse between the motor neuron and muscle fibre
ACh released into neuromuscular junction
An AP travels down the motor neuron; at the axon terminal Ca2+ channels open and the ions enter the axon terminal; triggers the vesicles containing ACh to fuse with the terminal membrane which releases ACh into the neuromuscular junction (synaptic cleft)
Activation of ACh receptors
The binding of ACh to the receptors on the muscle end plate causes opening of the ligand-gated ion channels; opening of these channels allows movement of predominantly Na+ into the muscle cell and depolarises it; short lasting as ACh is broken down by an enzyme
A muscle AP is triggered
If sufficient ligand-gated channels are opened, the end plate potential reaches threshold; voltage-gated Na+ channels open and an AP is triggered; the AP is then propagated along the sarcolemma and int the T-tubule system
AP in skeletal muscle
Small increase in sodium ion permeability causes volatge-gated Na+ channels to open and the ions rush in - depolarisation; channels close and the voltage-gated K+ channels open - begins repolarisation; channels close and the RMP stabilises, concentrations of both ions is restored
Excitation contraction coupling
Transient depolarisation during AP in skeletal muscle is conducted into the interior of the cell by the t-tubules where is causes the calcium channels in the SR to open; this allows calcium to bind to the troponin, which changes shape and exposes tropomyosin; contraction can occur
Calcium released from the SR
AP is conducted down the t-tubules coming in close contact with the SR; results in voltage-gated Ca2+ channels in the SR to open, ions are released into the cytosol
Ca2+ binds with troponin
When Ca2+ concentrations reach a critical threshold, the myosin binding sites on the actin filaments are exposed, allowing the cross-bridge cycle to occur
Contraction ends
Calcium is actively pumped back into the SR via Ca2+ ATPase pumps; troponin moves back and covers the myosin binding site
Muscle metabolism: creatine phosphate
For brief periods (<15s), creatine phosphate can act as an ATP store; creatine phosphokinase transfers Pi from Creatine-Pi to ADP to give ATP; anaerobic
Anaerobic glycolysis
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
Aerobic metabolism
Efficient, but comparitively slow; requires oxygen, therefore good blood supply; max 300W; important for postural muscles and endurance exercise
Control of muscle tension
Increasing the frequency of stimulation (number of APs in one motor neuron); recruiting additional motor units
Type 1 muscle fibre
Slow fibres which have a low maximum ATPase rate and lower maximum force production; mainly oxidative in metabolism and have large amounts of myoglobin and mitochondria (red colour); have extensive high energy phosphate stores which are replenished by slow aerobic metabolism; slow twitch
Type 2A muscle fibre
Fast fibres that have a high ATPase rate; can have a high oxidative capacity and glycolytic capacity in metabolism; have very large amounts of myoglobin and mitochondira (red colour); high oxygen demand is offset by them having small diameter to facilitate diffusion of oxygen across the cell; fast twitch
Type 2B muscle fibre
Not common in humans; fast fibres that have a high ATPase rate but low oxidative capacity; primarily glycolytic in metabolism with low amounts of myoglobin and mitochondria (white colour); large diameter makes them fatigue rapidly but generate large forces
Type 1 muscle fibre e.g.
Maintaining posture, walking; low intensity exercise; units with neurons innervating the slow efficient aerobic cells
Type 2 muscle fibre e.g.
Jumping, weight lifting; high power output exercise; units with the neurons innervating the large fibres that fatigue rapidly but develop large forces
Rate of stimulation
A single stimulus is delivered and the muscle contracts and relaxes; if another stimulus is applied before the muscle relaxes completely, the more tension results; temporal/wave summation, results in unfused/incomplete tetanus; at higher stimulus frequencies, there is no relaxation at all between stimuli and this is fused/complete tetanus
Temporal summation
Occurs when there is an increased frequency of APs; a twitch lasts longer than an AP
Recruitment
As more motor units are recruited to innervate a number of muscle fibres, the amount of force developed increases; generally, small oxidative motor units are recruited first and fewer large glycolytic motor units are recruited last; contractile function can be graded by recruitment of different motor units
Cardiac muscle
100um long; branched; myogenic (involuntary); atrial cells joined to each other by gap junctions that allow electricity to spread from one cell to the next, no t-tubules and contract relatively weakly; ventrical cells are branched and have numeroid gap junctions that join them to form sheets that divide and wrap around the ventricles, well developed t-tubule system occurs at level of z-discs
Heart
Cardiac muscle cells are found mostly in the left ventricle; heart has numerous mitochondria and myoglobin; primarily oxidative and deep red; each cell has 1-3 nuclei and growth occurs mainly through hypertrophy with little cell division
ventricular muscle cells
100um x 30um; 1-3 nuclei; lots of mitchondria; needs lots of oxygen for oxidative metabolism; SR not as extensive as skeletal muscle
Intercalated discs
Desmosomes prevent cells from seperating during contraction; contain gap junctions that allow the APs to be carried from one cell to the next; allows for co-ordinated contraction of all the myocytes (unlike skeletal where fibres are recruited by motor neurons)
Sino-atrial node
Group of specialised cells in the right atria of the heart where APs are initiated
Ventricular myocyte AP
AP initiated in sino-atrial node, spreads throughout the atria and then via specialised conducting cells to the ventricles; AP is long lasting (>100ms) due to presence of additional ionic currents that hold the cell depolarised for a period comparable to that of a twitch (heart beat); has plateau phase due to presence of large sustained Ca2+ current
Re-excitation of cardiac muscle
Membrane is highly polarised during most of the twitch and so it is unlikely that re-excitation will occur - the cells are refractory; troponin only has one calcium binding site so the calcium transient is of much lower amplitude than skeletal - leads to troponin not being fully staurated
AP vs contraction in skeletal vs cardiac
Skeletal: brief AP done before contraction, which is longer
Cardiac: long AP done at the same time as contraction
Stages of AP in cardiac muscle cell
Rapid depolarisation due to fast opening of voltage-gated Na+ channels
Plateau please due to slow opening of voltage-gated Ca2+ channel
Repolarisation due to closing of Ca2+ channels and opening of K+ (outward) channels
Structural basis for EC-coupling in ventricular cardiomyocytes
LTCC: L-type volatge-gated calcium channel
RyR: ryanodine receptor (calcium channel in SR)
NCX: sodium/calcium exchanger
NKA: sodium/potassium ATPase
Cardiac muscle EC-coupling 1
Depolarisation opens voltage-gated fast Na+ channels in the sarcolemma; reversal of membrane potential; depolarisation wave opens slow (L-type) Ca2+ channels in the sarcolemma (DHPR); Ca2+ influx balanced by a Na+/Ca2+ exchanger
Cardiac muscle EC-coupling 2
Ca2+ influx triggers opening of Ca2+ sensitive channels in the SR, ions flow into cytosol; raised intracellular Ca2+ concentration allows Ca2+ to bind to troponin and this switches on the contractile machinery
Relaxation in cardiac muscle
Ca2+ transport out of the cytosol with SR Ca2+-ATPase and sarcolemmal Na+/Ca2+ exchange
Regulation of cardiac output
CO (how much blood comes out of the heart) = SV (stroke volume) x HR (heart rate)
Heart rate
Set by the pacemaker cells in teh sin-atrial node; rate can then be modified, especially via the autonomic nerves releasing NTs
Stroke volume
Reflects the tension developed by the cardiac muscle fibres in one contraction
Pacemaker cells
In SA and AV node; slow depolarisation due to If current; depolarisation where Ca2+ channels open at threshold, produces rising phase of AP sustained opening of slow Ca2+ channels; repolarisation due to Ca2+ channels inactivating and K+ channels opening
Autonomic innervation of the heart
Vagus nerve: parasympathetic which decreases heart rate and releases ACh
Sympathetic cardiac nerves: increase heart rate and force of contraction (release noradrenaline)
Regulation of contractile force in cardiac
Increase rate of firing (automaticity); increase the dimensions of the ventricle (stretch); use NTs to alter rate and calcium handling (direct and rate effects)
Modulation of force with automaticity
Change in amplitude of the calcium transient whcih modulates the availability of actin binding sites for myosin and the number of attached cross-bridges; Ca2+ from previous AP that hasn’t left the cytosol yet can be used for the next AP
Modulation of force with muscle length
When length is suddenly increased, there is an immediate increase in force development due to the increased interaction between actin and myosin followed by a slow increase in the amplitude of the calcium transient over several beats
Modulation of force by NTs
Sympathetic cardiac nerves: increase heart rate and force of contraction (release noradrenaline)
Parasympathetic cardiac nerves: release ACh which slows the discharge of SA cells and reduce heart rate which decreases the force of contraction
Length-tension relationship skeletal vs cardiac
Active tension are the same; passive tension is different (more resting tension in heart) so the total tension is greatest in cardiac
Neural control of stroke volume
Noradrenaline released by sympathetic nerves leads to increased cytosol calcium due to increased heart rate shortenening time for extrusion; more Ca2+ comes into cell during AP and more released from SR; increased sympathetic stimulation results in increased output at any filling pressure due to increase in inotropy and heart rate
Smooth muscle found
Airways; bladder and reproductive organs; blood vessels; iris and ciliary muscles in eye
Structure of smooth muscle
Very long and thin with a singal central nucleus and tapered at the ends (spindle shape); may be connected to each other by dense bodies or by gap junctions and groups of cells may be electrically connected; considerable shortening can occur because contractile machinery is poorly organised; SR is poorly developed and spread throughout the cell; no troponin and t-tubules
Single unit smooth muscle
Sheets of cells that are electrically coupled and act in unison (as one unit); often spontaneously active; found in most blood vessels and hollow organs
Multi unit smooth muscle
Tissue made of discrete bundles of independent cells which are densely innervated and contract only in response to its innervation; vas deferens, iris, piloerectors
Initiation of contraction smooth muscle
Ca2+ ions enter cytosol from EC fluid via voltage-dependent or voltage-independent Ca2+ channels or SR; ions bind to and activate calmodulin which then activates myosin light chain kinase (MLCK; enzyme); MLCK activates the myosin by phosphorylation it which activates the myosin ATPases; activated myosin forms cross bridges with actin of the thin filaments and shortening begins
Relaxation in smooth muscle
Contraction ends when a myosin light chain phosphatase dephosphorylates the myosin light chain; Ca-ATPase in cytoplasm membrane reduces intracellular Ca2+
Arrangement of smooth muscle in hollow organs
Outer longitudinal layer and an inner circular layer; are at right angles to each other
Basic cellular structure of smooth muscle
No t-tubules (cavolae instead to increase the SA and helps get more APs into the centre); dense bodies (act like z-lines to anchor actin to sarcolemma); gap junctions electrically connect the cells together; intermediate filament is cytoskeleton element; poorly developed SR
Regulation of calcium in smooth muscle
Via voltage, hormones, neurotransmitters and specific ions; calcium source is from EC membrane and SR
Activation of myosin by MLCK smooth
Myosin does not hydrolyse ATP unless it is first phosphorylated; MLCK phosphorylates the light chain in the presence of the activated calmodulin
MLCK and MLCP smooth
Increased MLCK activity (Ca2+ regulated) will facour contraction; increased MLCP activity will favour relaxation; when intracellular Ca2+ drops, MLCP activity will dominate
Modulation of smooth muscle contraction
Stretch; neurotransmitters; hormones; environment; histamine; adenosine; prostacyclin; nitric oxide
Innervationof smooth muscle
Autonomic nerve fibres branch and form diffuse junctions with underlying smooth muscle fibres; varicosities in the terminal axons contain NT; NT is secreted into matric coating and diffuses to the muscle cells
Smooth muscle response to stretch
It will initially contract, effectively resisting the stretch, stretch-activated calcium channels; over time will slowly relax and adapt to the change in length via calcium-dependent K+ channels, hyperpolarising the membrane potential
