L.2, L.6 Cardiac muscle cell Flashcards
Describe the ultrastructure of cardiac muscle: What cell types make up myocardium
- Cardiac fibroblasts: most cells, important for secreting and maintaining CT
- Myocytes: 30% cells, majority of mass
- Carry out the contraction, includes purkinje and nodal cells (specialised cells)
- Endothelial cells: vascular and endocardial- important for cell signalling
- Vascular smooth muscle cells-.
- Neurons
Why are the gap junctions at intercalated discs important between myocytes
- allow electrical impulses and cytosolic continuity for function of the heart, need to have the contractions passed on to stop myocytes separating from neighbour
Myocyte is striated due to arrangement of myofibrils and contains a lot of contractile proteins and mitochondria. What are T tubules and Sarcoplasmic reticulum (SR)
T tubule: invaginations of cell membrane, allows AP propogation to the centre of the cell. Longitudinal T tubules connect myocytes as well.
SR is intracellular calcium store. wraps around half of the t-tubules= junctional SR. Between the two membranes are the Ryanodine receptors 2 (SR calcium release channels)
What is Excitation contraction coupling
The processes by which the electrical changes that occur during the AP at the surface membrane at the T-tubules that lead to calcium release into the cytosol from the SR. This calcium release allows cross bridge cycling to occur
What are the 5 steps in EC coupling
- AP propagated down from adjacent cell which spread across the SL.
- Depolarises membrane. Voltage gated Ca2+ channels open—called DHPR or Ltype Ca2+ channels
- Small influx of extracellular ca2+ current triggers open of Ryr calcium channels on the SR. This leads to large influx of Ca+ from the SR. (intracellular)
- Ca2+ intracellular concentration increases 10x. Ca2+ ions bind to TroponinC on myofilaments and initiate crossbridge cycling
- This leads to contraction of the myocyte.
What are DHPRs
DHPRs: voltage dependent ca2+ channel that contribute to the AP plateau, trigger EC coupling and are inhibited by SR Ca release
- Activated by depolarisation >-40mv
- Stimulated by catecholamines
- Inhibited by dihydropyridines and Mg2+, low plasma Ca+ which helps them stay shut in diastole (and vice versa)
What is the relationship between the initial Ca influx and the triggered Ca release from the SR
There is a dose response for Ca initiated Ca Release: more calcium current = more ca released= more forceful contraction.
However when SR Ca2+ load is high, there is increased Ca2+ available for release from SR for any given trigger and therefore enhanced gain of EC coupling.
*also more Ca helps to increase production of ATP: to match energy supply to demand.
Why is Ca homeostasis important?
For relaxation to occur intracellular ca2+ must be restored to resting (diastolic levels) that is ca2+ in = ca2+ out.
What triggers myocyte relaxation and what 3 things happen afterwards.
- Occurs when [Ca2+] in the cytosol is reduced and this causes Ca2+ unbinds from TnC
- Bulk of Ca2+ that was released is returned to the SR to storage, with a small amount leaving the cell in exchange for Na+ at the cell membrane (via NCXchange) equal to the amount that enters the cell due to the current.
- Na+ intracellular concentration gradient (low Na inside, high outside) is maintained by Na/K/ATPase which pumps out one net positive charge out the cell in each cycle
What takes Ca2+ back to the SR to induce myocyte relaxation and how is this inhibited/promoted
SRCaATPase: (SERCA).
Phospholambin inhibits the rate that SERCA takes up calcium. (inhibit)
Sympathetic activation phosphoryates phospholambin and stops this inhibition (promote uptake)–> leads to increased SR load.
What are the two minor transports for moving Ca2+ out of the cell and moving it into mitochondria
- SL CaATPase: Ca out of cell – minor contributor during diastole to maintain low concentrations of Ca in the cytosol. Uses 1 ATP: 1 Ca.
- Mitochondrial uniporter: Ca into mitochondria
What is the Ca transport method that can go both ways
- SL Na/Ca exchanger : 1 Ca :3 Na+
Operation depends on the Na gradient usually maintained by NaKatpase
- After AP it helps to take out Ca2+ because there is too much Ca2+ inside and not enough Na as well as -ve membrane potential
- During the early AP, it helps to bring in Ca2+ because there is too much Na inside, not enough Ca inside and +ve potential
How does starlings law of the heart modulate cardiac contraction (biphasic response to stretch)
An increase in EDV increases stroke volume as stretch increases myofilament sensitivity to Ca2+ binding tropnin C
- rapid: myofilament properties of increase in sarcomere length increases number of crossbridges formed
- Slow force response: increased Ca2+ influx due to signalling pathway activated by stretch
How does increasing heart rate affect heart contraction
When Increase AP there is less time for Ca2+ extrusion during diastole, there is a decrease in the average membrane potential which decreases overall Ca2+ efflux via NCX and there is increased influx of Ca2+ and Na+ with every AP so
Overall the amount of Ca2+ taken up and released by SR and the amplitude of the calcium transient increases
How does B- adrenergic stimulation by the sympathetic NS affect the heart contraction
- force, rate of relaxation, and increase of HR
Stimulates adenylyl cyclase –> increases cAMP levels. This activates cAMP dependent protein kinase (PKA) which phosphorylates
- Phospholambin which stops inhibiting SERCA uptake of Ca2+
- Troponin 1 which decreases myofilament Ca2+ sensitivity (compensated by Ca2+ transient effects)
- SL Ca2+ channels increases transient Ca2+
- SR Ca2+ release channels -alters the Ryr gating
