Electrical properties of the heart

These are integral to myocardial function.

1 alpha subunit, 2 beta subunits, 2 activation (M) gates, one inactivation (H) gate.

One can pretend that the gates are named for the shape the channel makes, see? (Actually they are just algebraic terms in the hodgekin-huxely model).

In resting state, the M gates are closed, sodium cannot flow, and the gate looks like an M.

As membrane voltage hits the threshold of -50, the M gates open in a sliding helix action, and sodium can flow into the cell, dragging the cell towards the sodium Nernst potential (+70mV). This is the open state.

After one to two ms, the H gate closes. This is the inactivated state. It lasts around 140ms, before the M gates once again close; repolarization then opens the H gate, returning the cell to the resting state.

These states correspond to the refractory periods of the cell:

The absolute refractory period is phase 0, 1, and 2, and part of phase 3. In this phase, the sodium channels are all either open (and the cell is maximally depolarized) or in inactivated state.

During the relative refractory period at the end of phase 3, some of the sodium channels are resting, but some are still inactivated, so any stimulus will produce a subnormal action potential.

The effective refractory period is the absolute refractory period plus part of the relative refractory period where any depolarization will be too small to spread to adjacent myocardium.

These have a fast upstroke, which facilitates a very fast conduction velocity of 50cm/s (the heart is about 12cm long, so that's about 240ms, or a wide QRS.) Purkinje fibres are faster, about 200cm/s.

Phase 4: Resting potential. -90mV. Maintained by

1. Na/K ATPase pump exporting charge and maintaining K+ gradient
2. Ik1 inwards-rectifying channel, which drags the membrane potential towards the K+ Nernst potential
3. The Gibbs-Donnan effect generated by impermiate intracellular proteins

Phase 0: Fast depolarization:

1. Positive charge leaks into the cytosol via gap junctions at intercalated disks until the threshhold of -65mV is reached.
2. Fast sodium channels open, and sodium floods in, spiking the Vm to +30mV

Phase 1: Early repolarization

1. Outwards flux of potassium via the voltage-gated Ito channels
2. Restores the Vm to 0mV

Phase 2: Plateau

1. Potassium efflux continues
2. L-type calcium channels open
3. Calcium influx = potassium efflux, no change in Vm
4. Lasts about 120ms

Phase 3: Repolarization

1. L-type potassium channels are inactivated by rising intracellular calcium
2. Ikr, Ik1 channels open
3. Vm drifts back to....

Stage 4: Resting potential (-90mV).

These have a slow conduction speed, about 5cm/s. But! They show initiative AKA automaticity.

Phase 4: Resting potential, -60mV. There is a slow inward Na+ current through \(I_f\) channels, resulting in a gradual increase in membrane potential until it hits a threshold of -40mV, then...

Phase 0: A slow, slow upstroke owing to the absence (or blockade of) fast sodium channels, mediated by special T-type calcium channels causing calcium influx, until the usual L-type calcium channels can take over.

Phase 1: N/A

Phase 2: N/A

Phase 3: Slow repolarization by Ikr and Ik1 channels

Cardiomyocytes with automaticity potential exhibit overdrive suppression.

1. Frequent depolarizations (e.g. due to SA nodal impulses) increase intracellular sodium
2. This increases sodium export via the Na/K ATPase, which hyperpolarizes the cell (because 3Na/2K ATPase exports charge)
3. The If current is constant, so it takes a longer time for these cells to reach their threshold potential.
4. Once the overdrive stimulus is removed, the resting potential is allowed to drift up until the cell becomes a pacemaker

During phase two of the cardiac action potential, calcium enters the cell. This sets off a chain of events:

1. The action potential propagates along the membrane and down the t-tubules, letting calcium all up into the cell via L-type calcium channels
2. The calcium then binds to the calcium-gated ryanodine calcium channel (yep) on the sarcoplasmic retuculuum surface
3. Masses of calcium burst forth. This is the final common pathway for all excitation-contraction coupling in all muscle cells
4. Calcium binds to troponin C, which moves tropomyosin out of the way of the actin binding site

While the actin binding site is exposed, myosin does its thang:

1. At rest, myosin is bound to an actin binding site with head flexed
2. Myosin binds an ATP, dissociating from actin
3. Myosin hydrolyzes the ATP, unflexing its head (its higher energy state)
4. Myosin binds to the new actin binding site
5. Myosin ejects the phosphate and flexes its head, sliding the actin fiber towards the H zone
6. Myosin ejects the ADP.

This shit continues ad nauseam until the calcium gets removed.

Mechanism 1: SERCA (Sarcoendoplasmic reticulum calcium ATPase)

Active transport of Ca2+ into the sarcoplasmic reticulum. Normally these have the breaks on in the form of an inhibitory protein called phospholamban (thank you ma'am). Protein kinase A, which gets activated by B1 agonism, phospophorytes and cleaves off phospholamban, which improves lusitropy. These consume heaps of ATP, about half of the muscle's ATP usage!

Mechanism 2: Buffering

To negatively charged proteins like paralbumin

Mechanism 3: Na/Ca ATPase

Exports the calcium extracellularly