Skeletal + Cardiac Myocytes Flashcards
what is skeletal muscle adapted to?
fast, powerful contractions to move limbs
what is smooth muscle adapted to?
slow, sustained contractions
what are the differences in excitation-contraction coupling between cardiac and skeletal muscle?
the mechanisms involved in the initiation of contraction
skeletal: end plate potential: needs impulse from somatic NS
cardiac: pacemaker potential: variations in membrane Na+, Ca2+ and K+ permeabilities
what is the main source of calcium for ECC in skeletal muscle?
reliant t tubules that mediate mechanical coupling
depolarisation due to AP induces conform change in DHP channels, directly propagated to RyR on SR, opens them and allows Ca2+ to enter cytosol
what is the main source of calcium for cardiac muscle contraction?
Ca2+ enters through DHP receptors and initiates intracellular signalling cascade
activates PLC, breaking down phosphatidylinositol phosphate to inositol 1,4,5 phosphate (IP3) and diacylglycerol (DAG)
IP3 binds IP3 dependent Ca2+ channels on the SR, allows Ca2+ to enter cytosol
primary source = extracellular
what is the mechanism of cross-bridge cycling in cardiac and skeletal muscle?
4 Ca2+ bind to troponin C (Ca2+ binding subunit of troponin), causing conform change that propagates through to tropomyosin binding subunit (T)
pulls troponin T out of myosin binding site on f actin, allowing cross bridges to form
- ATP binds myosin head, detaches head from actin monomer
- myosin head hydrolyses ATP to ADP + Pi: mysoin returns to original conformation, can now reach further along f actin to next but 1 monomer
- cross bridge forms as myosin rebinds actin
- Pi is released: myosin can change conformation + pull actin towards M line to push thin filament towards centre of sarcomere and bring Z disc proteins closer together
- ADP is released: filaments remain in attached state until next ATP binds
describe the structure of the thin filament
double chain of f actin molecules in helix structure assoc with tropomyosin (sits in the groove)
1 strand has spec amino acids which can contact myosin head
every 35nm there is trimeric troponin complex (T, C, I)
describe the structure of the thick filament
myosin tetramer w 2 heavy chain (each with head region a ATPase activity and tail that makes up bulk of filament)
2 smaller regulatory chains on teh heads
what is the relative organisation of thick and thin filaments?
each thick filament contacts 6 thin filaments around it by its myosin heads
why does the skeletal muscle method of Ca2+ sourcing for contraction not work in cardiac muscle?
no mechanical coupling of RyR to DHP (dihydropyridine)
how is skeletal muscle depolarised?
depolarisation from somatic NS
2 ACh mols released at NMJ bind alpha subunits of pentameric type 1 nicotinic receptor on the sarcolemma: causes influx of Na+ that depolarises muscle cell
briefly, how is cardiac muscle depolarised?
by pacemaker potentials
mediated by slow increases in membrane Na+ and Ca2+ permeabilities and decreased in K+ permeability
upon repol, K+ channels close and non-spec cation channels open, facilitating influx of Na+, gradually depolarising cell
this depol opens v.g. Ca2+ channels, allowing Ca2+ in, further depolarising
what are the phases of cardiac muscle depolarisation in ventricular myocytes?
phase 4: no current flowing
phase 0: driving force of upstroke = influx of Na+ and Ca2+
phase 1: fast and brief repol as Ca2+ & Na+ channels close rapidly + almost entirely
phase 2: channels reopen, sustained influx of Ca2+ determines plateau phase
phase 3: K+ channels open = repol + closing of remaining Ca2+ and Na+ channels
also draw the diagram
what determines the pacemaker current?
sum of inward I(Ca), outward I(K), inward I(f), background Na+ leak inwards and the NCX
RMP is already less -ve in SAN and AVN myocytes
what happens if you slow down the pacemaker potential?
takes longer to reach threshold where v.g. Ca2+ opens, longer for AP to be fired, less frequent APs
what are the phases of the AP in SAN myocytes?
phase 4: unique to cells of conduction system: spontaneous depolarisation occurs due to inward I(f): flow of Na+ inwards (channels opened on hyperpol)
progressive depol occurs until
end of phase 4: membrane is brought up to threshold where v.g. Ca2+ channels open
phase 0: rapid upstroke
phase 3: K+ channels open = repol + closing of remaining Ca2+ and Na+ channels
why is relaxation necessary in cardiac myocytes?
allows for ventricular filling
do not want summation as heart would just be constantly contracted
therefore cannot generate 2nd AP until 1st one is over and returned to RMP
what is the mechanism of relaxation of skeletal muscle?
mediated by removal of Ca2+ from sarcoplasm
through AT of Ca2+ into the SR by SERCA
some Ca2+ also pumped into extracellular material by Ca2+/H+ pump (PMCA) and Ca/Na exchanger (NCX) on sarcolemma
K+ leak channels on saarcolemma open to allow K+ efflux, depol cell, prevents further Ca2+ efflux from SR
what is the mechanism of relaxation of cardiac muscle?
same as skeletal: SERCA pump
phosphorylation of phospholamban (membrane-bound) removes inhibitory effect on SERCA, accelerating uptake
NCX linked to NKA, balancing [Na+] in cell
RoRelax also limited by affinity of TnC for Ca2+, Ca2+ extrusion from cell from NCX and number of crossbridges
what is Ouabain used for medicinally in the heart?
to generate more forceful contraction in heart failure
inhibits NKA, reduces Na pumped out, incr intracellular [Na+], reduces gradient, NCX works less efficiently, more Ca2+ left in cell, more Ca2+ available for contraction
what is the action of NKA?
3 Na+ out
2 K+ in
what is the action of NCX?
3 Na+ in
1 Ca2+ out
how is skeletal muscle contraction initiated?
end plate potentials triggered by AP from somatic motor neuron: cannot contract on their own
ACh released into synaptic cleft by exocytosis binds to nicotinic receptors on sarcolemma = influx of Na+
depolarises muscle fibril, leads to CaICaR
