Cardiac currents

Question 1

I [Na]

Answer 1

Produced by VGNaC
Responsible for depolarising phase (phase 0) of the AP.

NOT present in nodal cells. (In nodal cells, L and T-type Ca2+ channels generate ‘peak’, VGK+C result in repolarisation)

Question 2

I [Ca-L]

Answer 2

Produced by L-type Ca++ channels

Main current during the plateau (phase 2)

Question 3

I [Ca-T]

Answer 3

Produced by T-type Ca++ channels

Present in nodal & conductive tissue (not atria & ventricles)

Question 4

I [Na-Ca]

Answer 4

A result of the electrogenic activity of the Na+ / K+ exchanger (not a channel)
Removes Ca++ which has entered through Ca++ channels during the plateau phase from the cell
Activity affected indirectly by cardiac glycosides

Question 5

I [TO2]

Answer 5

‘Transient outward’
Produced by voltage gated K+ channels which activate rapidly in Phase 0 and then (unusually) inactivate rapidly.
Responsible (with I [T01]) for the ‘notch’ in the AP that constitutes Phase 1

Present only in ventricular tissue

Question 6

I [Ks]

Answer 6

Delayed rectifier
Result of 2 different K+ channels: KCNE1 and K[v]LQT2.
Mutations result in long QT syndrome

Question 7

I [Kur]

Answer 7

Delayed rectifier
Probably due to Kv1.5

Present in atria & ventricles (not nodal/conductive)

Question 8

I [Kp]

Answer 8

Plateau K+ current
Shows no particular rectification or voltage sensitivity.
Probably produced by twin pored channels of TWIK family

Present only in ventricle

Question 9

I [K1]

Answer 9

Inward rectifier stabilising the resting potential & preventing K+ loss. Most important current in maintenance of the resting potential.
Channels responsible have 2 membrane spanning domains, & are part of the Kir family

Present in atria & ventricles (not nodal/conductive)

Question 10

I [f]

Answer 10

Pacemaker current
HCN channels
- open on hyperpolarisation, close on depolarisation
- almost as permeable to Na+ as are to K+. Therefore on hyperpolarisation of the cell channels open - Na+ begins to enter, leading to a slow ‘drifting’ depolarisation up to the gating potential of the voltage gated channels.

Blocked by ivabradine
Present in nodal and conducting tissue

Question 11

I [Cl]

Answer 11

Chloride current
Probably a result of CFTR (expressed in abundance in the heart)
NB although CFTR is mutated in CF, CF sufferers do not, as a rule, have disordered cardiac function.

Present only in ventricle

Question 12

I [TO1]

Answer 12

‘Transient outward’
Produced by voltage gated K+ channels which activate rapidly in Phase 0 and then (unusually) inactivate rapidly.
Responsible (with I [T02]) for the ‘notch’ in the AP that constitutes Phase 1

Question 13

I [Kr]

Answer 13

Delayed rectifier
Probably produced by Kv11.1 channel, encoded by hERG gene.
Mutations -> long QT syndrome

Question 14

Delayed rectifiers

Answer 14

Activate with a ‘delay’ after depolarisation, and show little/ no inactivation.
Contribute outward current during the plateau- control timing of repolarisation (in Phase 3)
Blocking delayed rectifiers prolongs AP duration

Question 15

I [Cl]

Answer 15

Chloride current
Probably a result of CFTR (expressed in abundance in the heart)
NB although CFTR is mutated in CF, CF sufferers do not, as a rule, have disordered cardiac function.

Question 16

I [K-ACh]

Answer 16

Inward rectifier stabilising the resting potential & preventing K+ loss
Channel responsible: Kir 3.1, aka HGIRK1
Sensitive to ACh via M2 muscarinic receptors: channel activated by βγ subunit coupling directly to the channel.
When activated, effect is to hyperpolarise cardiac cells

Question 17

I [K-ATP]

Answer 17

Inward rectifier stabilising the resting potential & preventing K+ loss
ATP-sensitive K+ channels (K[ATP])
Channels close in presence of high levels of intracellular ATP (depolarising cell), open when ATP levels fall (hyperpolarising cell).

[NB also role in insulin secretion, present in vascular smooth muscle, may play role in ischaemic preconditioning]

Question 18

Inward rectifiers

Answer 18

‘Valve like’: Conduct inward K+ current v efficiently at hyperpolarised potentials, but close at depolarised potentials- preventing outward K+ current & K+ loss.

Occlusion producing rectification due to:

• intracellular Mg++ ions lodging in the pore
• intracellular polyamines (esp tetravalent polyamine spermine)