Cardiac muscle cells and their action potential

At threshold, voltage-gated sodium channels open and sodium rushes in down its electrochemical gradient, driving the upstroke. Potassium leaving drives repolarization.

• Potassium leaving through voltage-gated potassium channels:
• Correct: Sodium entering through voltage-gated sodium channels:
• Calcium entering through ligand-gated channels:

After opening, voltage-gated sodium channels inactivate. They cannot open again until the membrane repolarizes and their inactivation gates reopen, so no stimulus can start a new action potential.

• The sodium–potassium pump has stopped working:
• Correct: The voltage-gated sodium channels are inactivated:
• The cell has run out of sodium ions:

Calcium binds troponin, which shifts tropomyosin off the binding sites on actin so cross-bridges can form.

• Myosin heads:
• Tropomyosin:
• Correct: Troponin:

At threshold, voltage-gated sodium channels open and sodium rushes in down its electrochemical gradient, taking the membrane from about −70 mV to about +20 mV in about a millisecond. This is the same fast upstroke as in neurons and skeletal muscle.

• Calcium entering through L-type channels: L-type calcium channels open too slowly to carry a millisecond-long upstroke. Calcium entry holds the plateau that follows.
• Correct: Sodium entering through voltage-gated sodium channels: Correct. Fast sodium entry carries phase 0.
• Potassium leaving through voltage-gated channels: Potassium leaving makes the inside more negative. It carries repolarization in phase 3, not the upstroke.
• Calcium leaving the sarcoplasmic reticulum: Calcium released from the SR goes into the cytosol, not across the plasma membrane, so it does not change the membrane potential's upstroke. It activates contraction.

Blocking L-type channels shrinks the calcium trigger, so calcium-induced calcium release falls and each contraction weakens. The sodium upstroke is unaffected.

• Calcium entering the cell during the plateau: down. The blocked L-type channels are the path calcium takes into the cell during the plateau, so less enters.
• Calcium released by the sarcoplasmic reticulum each beat: down. Entering calcium is the trigger that opens the SR's release channels, so a smaller trigger opens fewer of them and less calcium is released.
• Force of each contraction: down. Less calcium in the cytosol binds less troponin, so fewer cross-bridges form and each contraction is weaker.
• Height of the phase 0 upstroke: no change. The upstroke is carried by sodium through voltage-gated sodium channels, which the drug does not block.

Charge from a neighbor brings the cell to threshold; the sodium upstroke depolarizes it; depolarization opens L-type channels; entering calcium opens the SR's release channels; the SR floods the cytosol with calcium; calcium binds troponin and the cell contracts.

• Correct order: 1. Charge flows in from a neighboring cell through gap junctions 2. The membrane reaches threshold and sodium channels open 3. L-type calcium channels open and calcium enters 4. Calcium opens release channels on the sarcoplasmic reticulum 5. The SR releases a large amount of calcium into the cytosol 6. Calcium binds troponin and cross-bridges form

The sodium channels stay inactivated through the whole plateau, so the absolute refractory period lasts about 200 to 250 ms, nearly as long as the contraction. No new action potential can start until the cell is already relaxing, so twitches cannot add up into tetanus.

• Correct: Its absolute refractory period lasts almost as long as its contraction: Correct. The long refractory period prevents wave summation and tetanus.
• Its sarcoplasmic reticulum holds too little calcium to sustain contraction: Even with a smaller SR, cardiac muscle cells get enough calcium for strong contractions. The limit is electrical, not a shortage of calcium.
• Gap junctions spread each stimulus so fast that no two ever overlap: Fast spread through gap junctions does not stop a cell from being restimulated. What stops it is that the cell cannot fire again until its refractory period ends.
• Heart muscle stores too little ATP to hold a contraction for long: Heart muscle makes ATP continuously by aerobic respiration. The lack of tetanus comes from the refractory period, not from an ATP limit.

A contractile cell fires only when charge from a neighbor brings it to threshold. That charge travels through gap junctions. With them closed, the charge cannot pass, so the neighbors stay at rest.

• The neighbors fire sooner, at a lower threshold voltage than usual: Closing gap junctions does not change a cell's threshold. It stops the charge that would reach it.
• The neighbors fire, but their plateau is missing: If a neighbor did fire, its own L-type channels would still produce a plateau. The problem is that it never reaches threshold.
• Correct: The neighbors do not fire, because charge cannot pass to them: Correct. Without gap junctions, the action potential cannot spread from cell to cell.
• The first cell stays depolarized and cannot repolarize: The first cell's own channels still work, so it repolarizes normally when its potassium channels open.

The shortest possible time between upstrokes is 0.2 s. That gives 1 ÷ 0.2 s = 5 per second, and 5 × 60 = 300 per minute.

• 200 per minute: 200 is the refractory period in milliseconds, not a rate.
• Correct: 300 per minute: Correct. 5 per second times 60 seconds is 300 per minute.
• 500 per minute: 500 per minute would mean one action potential every 0.12 s, which is shorter than this cell's 0.2 s refractory period allows.
• 120 per minute: 120 per minute would mean one action potential every 0.5 s, far slower than the refractory period allows.

In a human ventricle about three quarters of the calcium that activates contraction comes from the SR. The quarter that enters through L-type channels mainly triggers that release: calcium-induced calcium release.

• Correct: Most calcium comes from the SR; entering calcium is the trigger: Correct. The SR supplies most of the calcium; entering calcium triggers its release.
• All calcium comes from the SR; outside calcium plays no part: Outside calcium is essential. Without it there is no trigger, and the SR does not release its calcium.
• Half comes from the blood and half from the mitochondria: Mitochondria are not a source of calcium for contraction. The two sources are the SR and the extracellular fluid.
• Most comes from the blood, and the SR adds more only during fast heart rates: The SR is the main source at every rate, not an extra added at fast rates. Entering calcium acts as the trigger.