CVS - Cellular And Molecular Events

Question 1

Which pump DOES NOT set the resting membrane potential?

What is the role of this pump?

Answer 1

Na+/K+ ATPase (sodium pump)

To establish the gradients

Question 2

What are the concentration of ions intracellularly and extracellularly?

Answer 2

K+

Na+

Ca2+

Cl-

Question 3

How does the K+ permeability set the resting membrane potential?

How is the electrical gradient formed?

Answer 3

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

Question 4

When does the net outflow of K+ ions stop?

Answer 4

When the equilibrium potential is reached.

At Ek, there is not net movement of ions

Question 5

Why does the resting membrane potential not equal the equilbrium?

Ek -95mV RMP = -90mV

Answer 5

RMP is not as negative as Ek due to there being a small permeability to other ion species

Question 6

What is the role of cardiac myoctyes?

Answer 6

Fire action potentials

They are electrically active

Question 7

What does an action potential in a cardiac myocyte cause?

Why is this required?

Answer 7

Triggers an increase in cytosolic Ca2+

Increased is required to allow actin and myosin interaction

Question 8

Describe the ventricular (cardiac) action potential.

Be able to draw

Answer 8

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

Question 9

Why is the Ca2+ influx important?

Answer 9

For triggering contraction

Question 10

Describe the SA node action potential

What is the initial slope to threshold called?

Answer 10

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)

Question 11

Why is the upstroke in a SA node action potential not with Na+ ions?

Answer 11

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

Question 12

At what membrane potential is a pacemaker potential activated?

Answer 12

More negative than -50mV.

The more negative, the more it activates

Question 13

What are HCN channels?

What do they allow?

Answer 13

Hyperpolarisation-activated Cyclic Nucleotide- gated channels

Allow influx of Na+ ions which depolarise the cells

Only in pacemaker potential

Question 14

What does the pacemaker potential cause?

Answer 14

Slow depolarisation to threshold

By which time the Na+ channels will have been inactivated that’s why there is an influx of Ca2+ ions

Question 15

Which is the fastest node to depolarise?

What does it do?

Answer 15

SA node

Sets the rhythm, is the pacemaker

Question 16

What is the route of the SA node?

Answer 16

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

Question 17

Describe cardiac muscle

Answer 17

Striated muscle
Branching pattern
Single central nucleus
Cells connected at intercalated discs
Gap junctions

Question 18

What do gap junctions allow?

Answer 18

Movement of ions and electrical coupling of cells

Effectively large ion channels - allow rapid transfer of electrical activity between one cell and the other

Question 19

What do dermosomes do?

Answer 19

Rivet cardiac cells together structurally

Question 20

What effect does depolarisation have on the Ca2+ channels?

Answer 20

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

Question 21

What effect does the entry of Ca2+ have on the calcium induced calcium release channels?

Where are these channels located?

Answer 21

Opens the calcium induced calcium release channels in the sarcoplasmic recticulum

Question 22

What is the percentage of calcium that enters across sarcolemma and from sarcoplasmic recticulum?

Answer 22

25% enters across sarcolemma

75% released from sarcoplasmic recticulum (intracellular stores)

Question 23

What is the difference between the requirement for Ca2+ in skeletal muscle and cardiac muscle?

Answer 23

Skeletal muscle does not need an influx of Ca2+ as a conformational change can cause Ca2+ release

Cardiac muscle requires Ca2+ entry to contract

Question 24

Discuss excitation-contraction coupling in cardiac cells.

What pump is used to allow Ca2+ to go back into the SR?

Answer 24

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

Question 25

What type of t tubules are in skeletal and cardiac muscle?

Answer 25

Skeletal = triad Cardiac = diad

Question 26

What happens when calcium binds to troponin C?

Answer 26

Causes a conformational change, shifting tropomyosin to reveal myosin binding site on actin filament (Same as skeletal muscle) Revise sliding filament theory

Question 27

In relaxation what must happen to Ca2+? How is this achieved?

Answer 27

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

Question 28

How is the tone of blood vessels controlled? Where are these cells located? What cells are they present in?

Answer 28

By contraction and relaxation of vascular smooth muscle cells Smooth muscle cells located in tunica media Present in arteries, arterioles and veins

Question 29

What is the structure of vascular smooth muscle?

Answer 29

Actin and myosin filaments not sitting in nice striated pattern Actin and myosin filaments connected to dense bodies and radiate out

Question 30

Discuss excitation and contraction coupling in smooth muscle cells?

Answer 30

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

Question 31

What happens in terms of excitation contraction coupling when noradrenaline activates alpha 1 receptors? What inhibits MLCP?

Answer 31

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

Question 32

What must happen to the myosin light chain to enable actin-myosin interaction?

Answer 32

Must be phosphorylated

Question 33

What does phosphorylation of Myosin light chain kinase (MLCK) by Protein kinase A do?

Answer 33

Inhibits action of myosin light chain kinase Inhibits phosphorylation of the myosin light chain and inhibits contraction

Question 34

What initiates contraction of vascular smooth muscle cells?

Answer 34

Depolarisation or Activation of alpha adrenoreceptors

Question 35

How is the resting membrane potential set? What channels are open at rest?

Answer 35

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