CVS - Cellular And Molecular Events Flashcards
Which pump DOES NOT set the resting membrane potential?
What is the role of this pump?
Na+/K+ ATPase (sodium pump)
To establish the gradients
What are the concentration of ions intracellularly and extracellularly?
K+
Na+
Ca2+
Cl-
How does the K+ permeability set the resting membrane potential?
How is the electrical gradient formed?
K+ ions, more inside the cell than outside so they move down their concentration gradient
Small movement of K+ ions out of the cell leaves the inside of the cell -ve charged.
As charges builds up an electrical gradient is established
When does the net outflow of K+ ions stop?
When the equilibrium potential is reached.
At Ek, there is not net movement of ions
Why does the resting membrane potential not equal the equilbrium?
Ek -95mV RMP = -90mV
RMP is not as negative as Ek due to there being a small permeability to other ion species
What is the role of cardiac myoctyes?
Fire action potentials
They are electrically active
What does an action potential in a cardiac myocyte cause?
Why is this required?
Triggers an increase in cytosolic Ca2+
Increased is required to allow actin and myosin interaction
Describe the ventricular (cardiac) action potential.
Be able to draw
Upstroke due to opening of voltage gated Na+ channels (depolarise)
Initial repolarisation due to transient outward K+ channels
Plateau due to opening of voltage gated Ca2+ channels (repolarise). balanced with K+ efflux.
Repolarisation due to efflux of K+ through voltage gated K+ channels open. Ca2+ channels inactivated
Why is the Ca2+ influx important?
For triggering contraction
Describe the SA node action potential
What is the initial slope to threshold called?
Unstable membrane potential = Pacemaker potential- If (funny current) influx of Na+
Upstroke = Opening of voltage gated Ca2+ channels (depolarise)
Downstroke = Opening of voltage gated K+ channels (repolarise)
Why is the upstroke in a SA node action potential not with Na+ ions?
Na+ chanenls would have inactivated if they are slowly activated even by -60mV.
Very few Na+ channels in pacemaker cells
Note - initial pacemaker potential slow depolarise is with Na+ ions
At what membrane potential is a pacemaker potential activated?
More negative than -50mV.
The more negative, the more it activates
What are HCN channels?
What do they allow?
Hyperpolarisation-activated Cyclic Nucleotide- gated channels
Allow influx of Na+ ions which depolarise the cells
Only in pacemaker potential
What does the pacemaker potential cause?
Slow depolarisation to threshold
By which time the Na+ channels will have been inactivated that’s why there is an influx of Ca2+ ions
Which is the fastest node to depolarise?
What does it do?
SA node
Sets the rhythm, is the pacemaker
What is the route of the SA node?
Across right atrium
Down the septum
And up the bundle of his and up the sides of the ventricles - causing the ventricles to contract from the bottom
Describe cardiac muscle
Striated muscle Branching pattern Single central nucleus Cells connected at intercalated discs Gap junctions
What do gap junctions allow?
Movement of ions and electrical coupling of cells
Effectively large ion channels - allow rapid transfer of electrical activity between one cell and the other
What do dermosomes do?
Rivet cardiac cells together structurally
What effect does depolarisation have on the Ca2+ channels?
Opens the L type Ca2+ channels in the T tubule system
The Na+ ions depolarise the cell, this depolarisation causes the Ca2+ channels to open
What effect does the entry of Ca2+ have on the calcium induced calcium release channels?
Where are these channels located?
Opens the calcium induced calcium release channels in the sarcoplasmic recticulum
What is the percentage of calcium that enters across sarcolemma and from sarcoplasmic recticulum?
25% enters across sarcolemma
75% released from sarcoplasmic recticulum (intracellular stores)
What is the difference between the requirement for Ca2+ in skeletal muscle and cardiac muscle?
Skeletal muscle does not need an influx of Ca2+ as a conformational change can cause Ca2+ release
Cardiac muscle requires Ca2+ entry to contract
Discuss excitation-contraction coupling in cardiac cells.
What pump is used to allow Ca2+ to go back into the SR?
Excitation = Ca2+ moves into the cell
This opens the calcium release channel on the SR
Ca2+ is released from SR
Ca2+ from extracellular calcium goes on to bind to troponin C to trigger contraction.
Relaxation - need to remove Ca2+ from the cell, 25% goes out through channels, 75% goes back to SR through SERCA pump
What type of t tubules are in skeletal and cardiac muscle?
Skeletal = triad
Cardiac = diad
What happens when calcium binds to troponin C?
Causes a conformational change, shifting tropomyosin to reveal myosin binding site on actin filament
(Same as skeletal muscle)
Revise sliding filament theory
In relaxation what must happen to Ca2+?
How is this achieved?
Must return to resting levels
Most is pumped back into the SR via the SERCA pump
Raised Ca2+ stimulates the pumps
Some exits across the cell membrane via Na+/Ca2+ exchanger
Sarcolemma like Ca2+ATPase
How is the tone of blood vessels controlled?
Where are these cells located?
What cells are they present in?
By contraction and relaxation of vascular smooth muscle cells
Smooth muscle cells located in tunica media
Present in arteries, arterioles and veins
What is the structure of vascular smooth muscle?
Actin and myosin filaments not sitting in nice striated pattern
Actin and myosin filaments connected to dense bodies and radiate out
Discuss excitation and contraction coupling in smooth muscle cells?
Depolarisation opens the voltage gated Ca2+ channels –> influx of Ca2+–> binds to calmodulin–> activates MLCK (myosin light chain kinase) which phosphorylates the myosin light chain to permit interaction with actin
Relaxation as Ca2+ levels decline –> MLCP dephosphorylates myosin light chain, makes myosin inactive
What happens in terms of excitation contraction coupling when noradrenaline activates alpha 1 receptors?
What inhibits MLCP?
Causes production of Gq receptors –> stimulates IP3 –> causes release of calcium from SR–> calcium binds to calmodulin which activates MLCK to activate myosin
Protein kinase C
What must happen to the myosin light chain to enable actin-myosin interaction?
Must be phosphorylated
What does phosphorylation of Myosin light chain kinase (MLCK) by Protein kinase A do?
Inhibits action of myosin light chain kinase
Inhibits phosphorylation of the myosin light chain and inhibits contraction
What initiates contraction of vascular smooth muscle cells?
Depolarisation
or
Activation of alpha adrenoreceptors
How is the resting membrane potential set?
What channels are open at rest?
RMP is set largely due to K+ permeability of the cell membrane at rest
Leak K+ channels are open at rest
Na+/K+ ATPase pump DOES NOT set the RMP
