Cellular And Molecular Events In CVS (4)

Question 0

Describe a ventricular (cardiac) AP include timings and membrane potentials.

Answer 0

• Start at -90mv
• Na voltage gated channels open
• Causes an increase of membrane potential to +30mv at ~250ms
• Transient outward K current causes a dip to ~10mv (Na are inactivated)
• Ca voltage gated channels open
• Plateau as K efflux and Ca influx are fairly similar
• Repolarisation ~500ms at 0mv Ca channels become inactivated, voltage gated K channels open. (Takes ~100ms)

Question 1

How does the excitation of cells lead to contraction?

Answer 1

• Cardiac myocytes are electrically active
• AP is fired
• AP triggers an increase in cytosolic calcium
• An increase in calcium is required to all actin and myosin interaction.
• This generates tension and therefore contraction of the muscle.

Question 2

Describe a SAN AP

Answer 2

• Start at -60mv
• Pacemaker potential, influx of Na, slight slope
• ~-50mv Ca voltage gated channels open, causing an increase in membrane potential to peak at +30mv at around 700ms
• Voltage gated K channels open causing an efflux of K, membrane potential drops to ~-70mv (repolarisation)

Question 3

What is a HCN channel’s ability and how is this useful?

Answer 3

• Makes the threshold to reactivate Na channels more positive
• Hyperpolarisation activated
• Allows influx of Na ions
• cAMP sensitive

Question 4

How does the AP at the SAN differ from that of other AP in the heart?

Answer 4

• SAN AP is the fastest to depolarise
• Sets the rhythm - pacemaker
• Other areas are slower so can’t override SAN

Question 5

How can cytosolic Ca levels be increased in the heart?

Answer 5

• Depolarisation opens L-type Ca channels in T-tubule system
• Localised Ca entry, opens Ca induced Ca release (CICR) channels in SR
• 25/75 split (sarcolemma/SR)

Question 6

How is cardiac myocyte contraction regulated?

Answer 6

• Ca binds to tropanin C
• Conformational change shifts tropomyosin to reveal myosin binding sites on actin filament
• Sliding filament mechanism

Question 7

How do cardiac myocytes relax?

Answer 7

• Must return Ca to resting levels

- Most pumped back into SR via SERCA (increased Ca stimulates pumps)

Question 8

How is the tone of blood vessels controlled?

Answer 8

• Contraction and relaxation of vascular smooth muscle
• Tunica media
• Present in arteries, arterioles and veins

Question 9

How is regulation of contraction in VSM controlled?

Answer 9

• Ca binds to calmodulin
• Activates MLCK
• Phosphorylates the myosin light chain to permit interaction with actin
• Relaxation as Ca levels drop
• Phosphorylation by PKA inhibits MLCK - inhibits contraction