Electrical Properties

The cells in the myocardium are interwoven, may branch at either end, are joined at their boundaries by structures called __________ which contain ________

The cells in the myocardium are interwoven, may branch at either end, are joined at their boundaries by structures called intercalated disks which contain gap-junctions

Function of gap junctions

permit cell-to-cell conduction of excitation through intercalated discs

Explain the all or none rule in cardiac muscle

A stimulus arising at any point in the ventricle leads to the complete contraction of both chambers

Membrane permeability to Ca2+ is ______ (descriptor)

Very low

Membrane permeability to K+ is ______ (descriptor)

High

Membrane permeability to Na+ is ______ (compared to K+)

10% that for K + (small “inward background” current)

When K+ ions exit the cell, what is inside a cardiac myocyte that leaves behind a negative charge

cardiac myocyte contains negatively charged species (mostly organic phosphates and charged proteins), that cannot pass through the cell membrane

How do ions pass through cell membranes

Membrane channel

conductance (G)

The ease with which the ion passes through the membrane

How is ion conductance defined using R

1/R

R = resistance

G_K

G_Na

G_Ca

potassium conductance

sodium conductance

calcium conductance

i_K

i_Na

i_Ca

potassium current

sodium current

calcium current

What is required to happen for current to flow

If the conductance for an ion increases, the ion will pass through the membrane and a current will flow

resting membrane potential in contractile cells of the atria and ventricles is (in mV)

-90mV

what 2 things control resting membrane potential

the high concentration of potassium ions in the intracellular fluid

the high permeability of the cell membrane K + ions as compared to other ions

Equilibrium Potential for potassium (E_K+) in mV

-94mV

5 phases of cardiac action potential

Phase 0 Upstroke

Phase 1 Early repolarisation

Phase 2 Plateau phase

Phase 3 Late repolarisation

Phase 4 Resting membrane potential

Which ionic currents are at each place

The currents go in, out, in, out, in

i_to is K+ out

(NATO CAL(LED)! KK)

Phase 0 potential

-65mV

What happens in Phase 0

Membrane reaches threshold potential

Rapid flux of Na+ ions into the cell

Cell rapidly depolarises (1-2 ms)

Reaches a positive potential of +40mV

In phase 0 why doesn’t membrane potential reach E_Na

The outward potassium current is still flowing

(E_Na= equilibrium potential for sodium = 60mV)

Explain Phase 1 (why is the overshoot brief)

The overshoot is brief because the fast Na + channels are self- inactivating a decrease in G_Na

Within a couple of milliseconds the membrane voltage repolarises a few mV, owing to an outward current of K + ions (i_to)

What does the plateau in phase 2 represent

sustained depolarisation at a level slightly lower than peak depolarisation

What produces the plateau

a small sustained inward current of Ca2+ due to the opening of calcium channels (rise in Gca)

Talk about the flow of calcium in and out during the plateau

The calcium channels are voltage- operated channels, which begin to
activate slowly when the cells depolarises to reach their threshold of -30 mV to -35 mV (during rapid depolarization)

In the latter part of the plateau phase, calcium channels are beginning to inactivate
The inward current during this stage is due partly to sodium ions passing in through the sodium- calcium exchanger (Na-Ca exchanger)

What’s the significance of the long duration of the plateau phase (2 points)

1. The cell is electrically unexcitable / refractory for 200-400ms since active contraction of the cardiac muscle lasts only 200-250ms - a fused series of contractions is not possible in cardiac muscle (which would be fatal!)
2. The plateau phase not only initiates contraction but also directly influences the strength of contraction (greater Ca 2+ entry will give rise to stronger force of contraction)

At what mV does excitability return after the refractory period

Returns gradually when membrane potential is about -40mV

2 periods of refraction & duration of each

Absolute refractory period = 200 ms

Relative refractory period = 50 ms

What causes cardiac cells to be unexcitable during the refractory phase

the changes that occur to the fast Na + channel

The fast Na+ channel has 2 gates. What are they

the “m” gate – activation gate
the “h” gate – inactivation gate

(m = move gate. h = hold gate)

How does i_Ca almost stabilise the potential at 0mV to -20mV

The inward Ca+ current is almost sufficient to counterbalance the outward K+ current

Role of potassium in phase 3

The potassium conductance (G_K) increases towards the end of the plateau phase as the calcium channels inactivate

Potassium leaves the cell generating a potassium current (i_K)

This produces a repolarisation towards resting potential

What is phase 4

Resting membrane potential

(remember the phases are 0, 1, 2, 3, 4)

What does the excitation-conduction system consist of

Sinoatrial (SA) node

Atrioventricular (AV) node

Bundle of His

Left and right bundle branches

Purkinje fibres

Of the pacemakers which is dominant

SA node

How does generation of the action potential in the SA node differ from that of excitation of normal cardiac cells

It occurs spontaneously

Pacemaker cells have _____ resting potentials

unstable

The SA node action potential has only 3 phases.
What are they

Phase 4: Pre-potential or pacemaker potential
Phase 0: Upstroke
Phase 3: Repolarisation

initial potential of an SA node cell is about _______ and it _______ spontaneously

–60 mV to –70mV

declines (becomes more positive)

What is pacemaker potential (or pre-potential) - not a number - explain

slowly declining potential (becoming more positive)

What causes the decay of the pacemaker potential over time (2 causes)

An inward Na+ current - i_f (f is for funny)

The membrane becomes gradually less permeable to K+ (G_K) as the membrane depolarises.

The outward current i_K falls progressively allowing inward Na+ current (i_f)

The upstroke in the cells of the SA node is fast/slow in rising and big/small in amplitude

The upstroke in the cells of the SA node is slow in rising and small in amplitude

Main ionic currents in nodal pacemaker cells

_________ nervous system activity is generally responsible for changes in the rates of SA node discharge

Autonomic nervous system

The SA node is innervated with parasympathetic fibres & sympathetic fibres. What nerves correlate to each of these in relation to cardiac muscle

parasympathetic fibres = vagus nerve

sympathetic nerve fibres = cardiac nerves

Effect of parasympathetic stimulation on heart (2 points)

Reduces heart rate

Hyperpolarises the SA node - threshold is reached later - HR slows

How does hyperpolarisation occur

ACh binds to its receptor (muscarinic, M₂)

Activation of ACh - sensitive potassium channel (K_ACh) occurs

Potassium conductance (G_K ) is increased

When ACh binds to its receptor (muscarinic, M₂) it also has an effect on sympathetic stimulation. What is this effect

Binding of ACh leads to a fall in the intracellular concentration of cyclic AMP

This reduces the effects of sympathetic stimulation

Reduced i_f and i_Ca

Reduced slope of the pacemaker potential

Effect of sympathetic stimulation on heart rate

Increases HR

What does the release of noradrenaline (NA) indicate

Sympathetic stimulation

How does NA increase heart rate

Noradrenaline (NA) is released from sympathetic nerve endings

NA binds to β₁ adrenergic receptor - leads to a rise in intracellular conc. of cyclic AMP.

Increased intracellular conc. of cyclic AMP increases the i_f (inward Na+ current) & activates protein kinase A which phosphorylates the Ca channel & increases i_Ca (inward Ca²⁺ current)

Sodium (G_Na) and calcium conductance (G_Ca) are increased and inward calcium (i_Ca) and sodium currents (i_f) are increased

The slope of the pacemaker potential is increased

Role of protein kinase A in cardiac muscle cells

phosphorylates the Ca channel & increases i_Ca (inward Ca²⁺ current) - increases heart rate

phosphorylates the K channel involved in repolarisation

• increases the repolarising K+ current (i_K)

• Shortens the duration of the action potential

• Without this effect, the long duration of the cardiac action potential would begin to limit heart rate