Cardiac Muscle 1 Flashcards
General Features of Cardiac Muscle
Myogenic Striated Cells electrically coupled Mainly oxidative in metabolism AP triggers synchronised Ca2+ release from internal store SR (CICR)
Main cells types
Cardiac Fibroblasts Myocytes Endothelial cells Vascular SM Neurons
Cardiac Fibroblasts
Majority of cells in the heart
Secrete and maintain CT fibres
Myocytes
(~30% of all cells)
Majority of myocardial mass
Carry out myocardial work/contractions
Some are v specialised (purkinje&nodal cells)
What do myocytes look like?
- Striated (bundles of contractile proteins)
- have EC spaces containing collagen.
- Intercalated discs at intercellular junctions consisting of : Gap junctions, intermedite junctions and desmosomes
Extracellular space
-~33% heart volume
~60% vascular ~23% glycocalyx-like substance 7% CT cells 6% empty space 4% collagen
T-Tubules
- Formed by invagination of the sarcolemma.
- Allow for propagation of the AP to the centre of the muscle fibre, due to close interaction between the junctional SR and the sarcolemma (SL)
- Rich in DHPRs(slow, L-type calcium)
T-tubule ultrastructure, normal vs failing heart
Normal: RyR and DHPR can’t be discerned from one another as the junction between SR and SL is too small (to allow for sufficient CICR)
Failing: may channels that are not associated with the other, alters AP speed etc
E-C coupling
Electrical change @ surface membrane > changes intracellular calcium (via DHPRs and RyRs) > activate contraction
Rapid event.
Steps of Cardiac E-C coupling
1) Activation of Ica: AP propagates, depolarises membranes via sodium influx, DHPRs activated (L-type calcium channels)
2) Activation of CICR: small inflow of Ca (from DHPRs) activates much large CR, ‘calcium sparks’ from SR (via RyRs). This can occur as the two receptors are so closely associated to one another
3) Force Development: Ca diffuses to contractile proteins within the myocytes, binds to exposed troponin-C sites on the myofilament > X-bridge cycling
4) relaxation; when cytosolic levels of calcium return to normal
How does relaxation (returning of cytosolic Calcium levels) occur
1) reuptake by SR ‘SERCA’ (70-90%)
2) Na/Ca exchanger. 3Na in for 1Ca out. Electrogenic.
3) Ca ATPase in surface SL (1-2%)
4) Ca pump in mitochondria
Role of DHPRs
- Found on the sarcolemmal membrane (inc T-tubules), activated by membrane depol > carry Ica (inward Ca current)
- Contribute to AP plateau, via a small inward current
- Trigger E-C coupling by activating RyRs by CICR > much larger Ca2+ release
- Inhibited by SR calcium release
DHPRs activated by
Depolarisation of >-40mV
DHPRs stimulated by
Catecholamine
DHPRs inhibited by
Dihydropyridines (Ca channel blockers)
Mg2+
Low plasma
SR Role
Reservoir for intracellular Ca
- Ca buffered in SR by calsequestrin, a molecule that allows the SR to store an extraordinarily high amount of Calcium.
- 35-40 Ca ions per calsequestrin molecules
SR channels
- Ca release channels (RyRs), CICR > increased calcium transient
- SR Ca ATPase (SERCA) 2Ca:1ATP actively pumps calcium back into the SR (70-90% extrusion)
When SR Ca2+ load is high
Increased Ca available for release
-Enhanced gain of E-C coupling between DHPRs and RyRs (amount of Ca released from SR for any given Ica flow)
SR release events
Lots of “calcium sparks” from SR (that summate to make the whole calcium transient
The sparks amplitude and frequency determines the Ca transient amplitude
Summary of Contraction
1) AP from adjacent cell spreads over sarcolemma
2) DHPRs channels are activated/opened > Ica flow
3) Ica activated RyRs in the SR > Ca sparks which summate to calcium release
4) Calcium ions bind to Troponin-c on actin filaments and initiate x-bridge cycling
5) Contraction
Summary of Relaxation
1) Occurs when intracellular [Ca2+] is lowered, and ca2+ unbinds from TnC
2) Bulk of Ca actively pumped back into SR for storage (SERCA), with a small amount leaving the cell in exchange for Na+ (via NCX)
3) intracellular [Na+] gradient maintained by Na/K ATPase
Four important Ca transport proteins for Myocyte relaxation
SR Calcium ATPase SERCA (Ca > SR)
SL Calcium ATPase (Ca > out of cell)
SL Na/Ca exchanger (Ca > out of cell)
Mitochondrial uniporter (Ca> into mitochondria)
In steady state Calcium influx and efflux is balanced. What happens if Ca efflux is decreased
Calcium will accumulate
1) Higher SR calcium content
2) Next transient has increased extrusion to balance influx
Same will happen if influx is increased
SL Ca-ATPase
minor extrusion of Calcium
Uses 1ATP to remive 1 Ca
Likely to be electroneutral
Electrogenic NCX
carries one net charge per cycle. reverse mode (ca entry) follows depol > affects plateau
Forward mode (Ca extrusion) follow repol
So NCX contributes to the Vm
