Electrical & Molecular Events

Question 1

Describe how the resting membrane potential of cardiac cells is generated

Answer 1

Cardiac myocytes are permeable to K ions = electrical gradient set up = more –ve inside, more +ve outside

Question 2

What is the normal level of K+ inside and outside the cell?

Answer 2

140mM inside, 4mM outside

Question 3

What cell type has the longest AP?

Answer 3

Myocytes in the ventricle

Question 4

What is the RMP for an axon, skeletal muscle, SA node, ventricular myocytes?

Answer 4

-70, -90, -60, -90 respectively

Question 5

Draw the changes in membrane potential and describe the ionic currents underlying the cell action potential of ventricular cells

Answer 5

Question 6

Draw the changes in membrane potential and describe the ionic currents underlying the cell action potential of pacemaker cells

Answer 6

Question 7

How does an AP fire in a pacemaker cell?

Answer 7

Doesn’t need a nerve impulse, spontaneous depolarisation

Question 8

What type of Na+ channels in pacemaker potential cause an influx of Na+ and subsequent depolarisation?

Answer 8

HCN channels

= hyperpolarisation-activated, cyclic nucleotide-gated channels

Question 9

What sets the rhythm of the heart beat and why?

Answer 9

SA node = fastest to depolarise

Question 10

Describe the processes of excitation-contraction coupling in ventricular myocardial cells.

Answer 10

1 AP = 1 contraction:

APs = depolarisation to open plasma membrane L-type Ca2+ channels in T-tubule system = CICR (Ca induced Ca release) by SR = elevation in intracellular Ca2+ = binds TnC = shifts tropomyosin to reveal myosin binding site on actin = myosin can now bind

Question 11

Describe the factors influencing the changes in intracellular free calcium concentration of ventricular cells during the action potential

Answer 11

At certain MP Ca2+ channels will open = influx, influx will then cause CICR

Question 12

What happens if: AP too slow? AP fails? AP too quick? AP become random?

Answer 12

Bradycardia,

asystole,

tachycardia,

fibrillation respectively

Question 13

Explain the effects of hyperkalaemia on the heart

Answer 13

K+ >5.5mM:

myocyte AP = K+ potential gets less –ve = membrane depolarises a bit = inactivates voltage-gated Na+ chan = reduces Na+ chan available = slows upstroke (which requires Na+ influx) = risk of asystole.

Pacemaker AP = funny current (Na+ influx) lengthening due to inactivation of Na+ by high [K+] = heart rate slows

Question 14

What can you treat hyperkalaemia with?

Answer 14

Calcium gluconate = makes heart less excitable

Question 15

Explain the effects of hypokalaemia on the heart

Answer 15

K+ <3.5mM:

myocyte AP = lengthens AP = delays repolarisation (lower [K+] = takes longer to move back in) = can lead to early after depolarisations (EADs) = oscillations in MP = ventricular fibrillation VF = no CO

Question 16

How do cardiac myocytes relax?

Answer 16

Must return [Ca2+] back to resting levels = SERCA to SR, Ca2+ ATPase across cell membrane

Question 17

Outline the excitation-contraction coupling in the vascular system

Answer 17

NA activate α1 GPCR = activation of G α1 + then IP3 = release Ca2+ from SR = Ca2+ binds CaM (calmodulin), CaM then able to bind MLCK (Myosin light-chain kinase) = phosphate taken from ATP, added to myosin head = active.

Also DAG gets activated = PKC activated which stops MLCP (myosin light-chain phosphatase) from removing phosphate from myosin light chain (light chain must be activate = phosphorylated to enable actin-myosin interaction)

Question 18

How is contraction in the vascular system regulated?

Answer 18

MLCK can be phosphorylated by PKA = inhibition

Question 19

What is the normal plasma [K+]?

Answer 19

3.5 - 5.5