MODULE 3: muscle cells Flashcards
cardiac output
blood pumped by ventricle per minute (left and right ventricle have same CO)
CO = heart rate x stroke volume
during exercise: CO ~ 20-30L/min
at rest:
CO = 5L/min
HR = 70beats/min
SV = 70mL/beat
contractile properties of cardiomyocytes
adjacent cardiac cells are interlocked by:
- intercalated discs
- desmosomes (structures that anchor membranes together)
- gap junctions (allow ions to move between cells)
cardiac muscle cells electrically coupled –> function as single unit –> “functional syncytium”
note: atrial and ventricular cells not linked
different types of cells in myocardium:
- contractile cells –> mechanical work
- conducting/autorhythmic cells –> generate AP (~1%)
action potential in cardiac cells:
- graph
- ion channel activity
graph
at positive MP, na+ channels inactivated. channels reprimed for ~250ms
cardiomyocytes have L-type Ca2+ channels that are activated when MP becomes very positive –> keeps membrane positive for longer
at rest:
- K+ out
- Na+ in
- Ca2+ in
plateau phase:
- K+ out
- Na+ inactive
- Ca2+ in
repolarisation phase:
- K+ out
- Na+ in
- Ca2+ inactive
action potentials in SA node vs ventricular cell
graphs
(differences due to ion channel subtypes present in each cell)
SA nose AP has slow rise during rest phase to threshold as it controls autorhythmcity in the heart
ventricular cell AP has steady resting phase so it is only activated by sudden opening of Na+ channels
electrocardiography of heart beat
ECG not a direct recording of electrical activity in the heart
- SA node generates impulse –> atrial excitation begins
- impulse delayed at AV node
- impulse passes to heart apex –> ventricular excitation begins
- ventricular excitation complete
P-wave = atrial depolarisation Q-wave = impulse delayed R-wave = ventricular depolarisation S-wave = late ventricular depolarisation T-wave = ventricular repolarisation
graphs
effect of parasympathetic activity on the heart
- ach slows closure of K+ channels (fast acting)
- increases resting leakage of K+
- hyperpolarisation opposes normal decrease K+ permeability
- also slows opening of Ca2+ channels = slower depolarisation
- —-> takes longer to reach threshold
graph
at SA node:
- overall slows pacemaker activity
- decrease heart rate
at AV node:
- decreases node excitability
- increase AV delay
other effects:
- weakens atrial and ventricular contraction
- combo of brief latency period and rapid decay of response allows vagus nerves to exert a beat-to-beat control on heart rate`
effect of sympathetic activity on the heart
- noradrenaline decreases K+ permeability
- accelerates inactivation of K+ channels
- rapidly drift to threshold
- increased depolarisation rate plus NAd increases inward Ca2+ current
- —-> reaches threshold quicker
graph
structure/microstructure of skeletal muscle
muscles linked to bones via tendons through which force and movements developed during contractions are transmitted to the skeleton
unlike cardiac cells, not functionally coupled
each cell has own nerve supply
microstructure:
- contractile components take up >80% of cell
- T-tubules –> carries AP into cell
- sarcoplasmic & endoplasmic reticulum –> buffer Ca2+
- sarcomere –> actin, myosin, Z-line, M-line
calcium signalling in skeletal muscle
Ca2+ heavily buffered in cell by binding to proteins
Ca2+ + protein CaProtein (conformational and functional change
major Ca2+ binding sites in cell:
1) troponin C –> cytoplasm
2) parvalbumin –> cytoplasm
3) membrane-imbedded proteins –> both sides of membrane
4) calsequestrin –> inside SR (majority os calcium ions bind calsequestrin)
compartmentalisation of calcium ions in skeletal muscle
AT REST:
- extracellular [Ca2+] ~ 2 mM
- little Ca2+ bound to troponin C in cytoplasm
- lots of Ca2+ bound to calsequestrin in SR lumen
ACTIVATED
- extracellular [Ca2+] ~ 2 mM
- lots of Ca2+ bound to troponin C in cytoplasm
- lots of Ca2+ bound to calsequestrin in SR lumen
large gradients between extracellular, cytoplasm and SR lumen
large gradients maintained by pumps
low calcium concentration in cytoplasm allows mucles to rest
steps of excitation-contraction coupling in skeletal muscle
1) AP propagation along surface membrane
2) activation of voltage sensor (VS) in the t-system membrane
- DHPR (dihydropyridine receptor)
- forms L-type Ca2+ channel
3) different from cardiac mechanical activation of SR Ca2+ release channel by the VS
- note: VS not GPRC –> no second messenger
4) SR Ca2+ rapidly released into cytoplasm of cell, increasing concentration 100 fold in a few ms
5) Ca2+ binds to contractile protein and causes filaments to slide past each other = force
6) Ca2+ pumped from cytoplasm back into SR. Ca2+ unbinds from contractile proteins = relaxation
EC coupling: skeletal vs cardiac
diagrams
SKELETAL:
- DHPR acts as Vm sensor
- EC coupling more specialised in skeletal muscle
- mechanism (VDCR = voltage dependent calcium release):
- —> DHPR = L-type Ca2+ channel
- —> AP moves through T-tubule membrane, voltage sensitive cells depolarise, membrane changes conformation
- —> direct interaction between VS and RyR (calcium release channel)
- —> conformational change: DHPR makes protein-protein link w/ RyR to cause Ca2+ release
- —> Ca2+ released to cytoplasm
- —> some binds to contractile proteins, some binds to inactivation site on RyR
- —> when threshold of Ca2+ binds RyR shuts
CARDIAC:
- DHPR acts as Ca2+ channel
- cardiac SR holds less Ca2+
- larger T-tubules
- mechanism (CICR = calcium induced calcium release):
- —> in plateau phase, DHPR changes structure and Ca2+ enters via L-type calcium channel (keeps membrane depolarised)
- —> Ca2+ binds RyR (small amount)
- —> causes CICR
- —> VS opened for hundreds of ms and large amount of Ca2+ released
- —> bind to contractile proteins = force
- —> inactivation site in SR lumen
- —> Ca2+ moves from lumen to cytoplasm
- —> triggers closure when certain amount of Ca2+ lost from lumen
