striated muscles Flashcards
Troponin system
different sub units?
what do they bind to?
sit where?
Consists of three subunits
TnT – binds to tropomyosin
TnI – Binds to active actin sites – preventing myosin-actin interactions
TnC – Binds Ca2+
sits on the actin filament at the site where A + M will bind
Rise in Ca2+ activates tropomyosin–troponin system
what happens at resting Ca2+ levels?
what happens when Ca2+ levels rise?
Resting Ca2+ levels
Actin active sites are covered by tropomyosin held in place by troponin system (T, I, C)
Rise in Ca2+
Ca2+ binds to Trop-C,
Changing conformation of TnT-TnI-tropomyosin complex exposing actin active sites
Allowing myosin head to bind
What causes rise in Ca2+ to initiate contraction?
what receptors control skeletal muscle contraction? receptors for cardiac and smooth muscle contraction?
Receptors:
Recognise and bind drugs
Provide communication between extracellular and intracellular environments to produce biological response
Ligand-gated receptors control skeletal muscle contraction
AND
G-protein-coupled receptors control
cardiac and smooth muscle contraction
Skeletal Muscle - Nicotinic ligand-gated receptors at NMJ
what happens when nic receptors activated? by what?
how many sub units?
speed?
Activation of nicotinic ligand-gated receptors by acetylcholine (Ach) mediate communication between motor nerve and skeletal muscle at neuromuscular junction (NMJ)
Nicotinic receptors at NMJ composed of five different protein subunits and have extracellular binding site for Ach
Ach release - receptor activation - initiating muscle contraction
Very fast response - milliseconds (ms)
One of the reasons why movement occurs ‘instantaneously’
Skeletal Muscle - Activation of nicotinic receptors at NMJ
7 step process
- Conduction of action potential in motor nerves
- Activation of voltage-gated Ca channels and Ca influx
- Ca-dependent release of Ach
- Ach activates nicotinic ligand-gated receptors
- Generation of excitatory junction potential (EJP)
- Activation of voltage-gated Na channels, initiation of action potentials - contraction
- Breakdown of Ach by AchE– termination of response
Skeletal Muscle - How Ach-mediated EJP produces
action potential
what binds? effect? what enters?
Ach binds to Ligand-gated receptor
Channel opens
Na enters
Production of excitatory junction potential (EJP)
Reaches threshold for activation of voltage-gated Na channels
Initiation of upstroke
Skeletal Muscle - How Ach-induced action potentials produce contraction
where is Ap conducted? what does this activate?
where is there direct coupling? effect of this?
where does this bind? effect of this?
net effect?
1) Action potential conducted to t-tubule – activates VGCCs
2) Direct coupling between VGCCs and RyR on sarcoplasmic reticulum (SR) -> Opening RyR causes release of Ca
3. Ca binds to troponin C – allows actin–myosin interactions
4. Myosin heads perform power stroke
5. Contraction – actin filaments move toward centre of sarcomere
Cardiac Muscle - Action potentials conducted from pacemaker generate contraction
san conduction to?
what does AVN do? why?
bundle of his role?
(1) Conduction across both atrium to A-V node
(2) A-V node slows conduction rate (allows filling of ventricles before contraction), transmits activity to fast conducting pathway - Bundle of His
(3) Bundle of His - fast conducting pathway to purkinje fibres to allow both ventricles to be stimulated together
What generates the ap in the heart?
does it require nerve input?
intiated by?
Contraction of cardiac muscle is INTIATED by cardiac action potentials generated in specialised cells at the pacemaker called sino-atrial node
– DOES NOT require nerve input –
How does ap in the heart lead to contraction?
what will be activated? effect?
where will some of this act? effect? this is called?
net effect of this?
Voltage-gated Ca2+ channels will be activated hence there will be a Ca2+ influx. Some of the Ca2+ can act as ligands for the RyR receptors on the SR which will release Ca2+ from stores -> this is called CICR (calcium induce calcium release)
All the Ca2+ will be used for the troponin system + help with the sliding filament theory to bring about contraction
G-protein-coupled receptors - B1-adrenoceptors and heart
effect of this?
what is this central to?
used to maintain what? during when?
Although contraction of cardiac muscle is INTIATED
by cardiac action potentials
Activation of G-protein-coupled B1-adrenoceptors by
noradrenaline released from sympathetic nerves
and
circulating adrenaline released from adrenal medulla
INCREASE cardiac muscle contraction
VERY IMPORTANT response
e.g. Central to how we increase cardiac output/blood flow during exercise
Used to maintain blood flow during crisis – haemorrhage, septic shock
Clinically significance – many drugs used to regulate heart act at B1-adrenoceptors and associated signal transduction pathway
How does stimulation of B1-adrenoceptors
increase contraction of cardiac muscle?
what will bind to B1? what pathway does it activate? effect of this?
Na will bind to the B1 adrenoreceptor which leads to the activation of the Gs pathway so more ATP will be converted into More cAMP which will lead to more PKA which will phosphorylate the VGCCs so there is more of a CA2+ influx which will bind to the RyR receptors on the SR hence CICR and more Ca2+ is released which all leads to further activation of troponin and contraction
How is [Ca2+]i reduced to produce striated muscle relaxation
3 ways ca2+ removed?
effect of decrease in Ca2+?
Ca2+ uptake into SR - Ca2+-ATPase
Extrusion of Ca2+ from cell - Ca2+-ATPase Na-Ca exchanger
Decrease in [Ca2+ ]i
Reduced TnC-Ca2+
Tropomyosin binds to active actin sites
Prevents actin-myosin interactions
