Module 4 Study Guide
Everything above, compressed to what you should be able to reproduce without the slides in front of you.
Core ideas¶
The five-step template unifies all three muscle tissues: stimulation raises free calcium, calcium binds a regulatory protein, cross-bridges form and tension rises, calcium falls, tension falls. Only the details differ.
Smooth muscle regulates on the thick filament through myosin phosphorylation. Skeletal and cardiac regulate on the thin filament through troponin.
Smooth muscle’s calcium sensor is calmodulin. Cardiac muscle’s is troponin C, same as skeletal.
MLCK is the gas, MLCP is the brake. Every smooth muscle modulation raises one or lowers the other.
Smooth muscle depolarizes on calcium influx, not sodium.
Calcium-induced calcium release appears in both smooth and cardiac muscle. A small influx from outside triggers a large release from the sarcoplasmic reticulum.
Cardiac muscle borrows sarcomeres, troponin, and T tubules from skeletal muscle, and automaticity, autonomic innervation, coupling, and long waveforms from smooth muscle.
Cardiac automaticity is mandatory, not optional. Nerves modulate the pacemaker rather than command it.
The cardiac plateau exists because potassium leaving balances calcium entering. That calcium is what drives contraction.
Frank-Starling is cardiac length-tension, but the mechanism appears to be filament proximity raising calcium sensitivity, not filament overlap.
Sympathetic stimulation of the heart is strong and does four things at once: two raise contraction, two speed relaxation. Parasympathetic reverses all four weakly.
Cardiac muscle cannot be tetanized. Skeletal and smooth can.
Key terms¶
- Dense bodies
- Structural proteins anchoring smooth muscle thin filaments. Scattered, which is why there are no striations.
- Caveolae
- Shallow membrane indentations in smooth muscle holding most ligand receptors, membrane enzymes, and ion channels. Smooth muscle’s answer to T tubules.
- Phasic / tonic
- Baseline relaxed, contracts when needed / baseline contracted, relaxes when needed.
- Single-unit / multi-unit
- Electrically coupled, fires as one / independent, each cell separately innervated.
- Varicosities
- Swellings along an autonomic axon terminal that release neurotransmitter at many points.
- Gap junction
- Non-selective ion channel bridging two membranes, joining cytoplasm to cytoplasm.
- Peristalsis
- Circular and longitudinal layers alternating to push food down the digestive tract.
- Slow wave potential
- Graded-potential-like waveform in smooth muscle that spikes on reaching threshold.
- Automaticity
- Spontaneous, regular self-generated depolarization.
- CICR
- Calcium-induced calcium release. Calcium entering binds the ryanodine receptor, which releases stored calcium.
- Phospholipase C
- Enzyme that splits a membrane phospholipid into DAG and IP₃.
- IP₃ receptor
- Ligand-gated calcium release channel on the smooth muscle sarcoplasmic reticulum.
- Calmodulin (CaM)
- Smooth muscle’s calcium sensor, standing in for troponin.
- MLCK / MLCP
- Myosin light-chain kinase, phosphorylates myosin to activate it / phosphatase, dephosphorylates it to deactivate.
- Rho kinase
- Enzyme that inhibits MLCP, indirectly raising force.
- Nitric oxide
- Hydrophobic smooth muscle relaxant. Raises cyclic GMP, which raises MLCP.
- Calcium sensitization
- Leftward shift of the calcium-contraction curve. Same calcium, more contraction.
- Myocardium
- Cardiac muscle. Between the pericardium outside and endocardium inside.
- Intercalated disk
- Junction between cardiac cells, containing desmosomes and gap junctions.
- Dyad
- One sarcoplasmic reticulum patch plus one T tubule. Skeletal muscle’s triad has two patches.
- Frank-Starling law
- Resting cell stretch is proportional to active force production.
- Preload
- The heart-specific term for stretch on the muscle.
- Protein kinase A (PKA)
- Raised by cyclic AMP in cardiac muscle. Phosphorylates four targets.
- Phospholamban
- The brakes on the SERCA pump. Phosphorylating it releases the brakes.
- Troponin I
- Inhibitory subunit. Phosphorylating it speeds calcium dissociation from troponin C.
Numbers worth knowing¶
Smooth cell thickness | 5–10 µm |
Smooth cell length | 30–200 µm |
Cardiac cell thickness | 10–20 µm |
Cardiac cell length | 50–100 µm |
Skeletal cell length | 300,000 µm |
Endocardium | ~0.5 µm |
Pericardium | ~1 mm |
Myocardium | up to 9 mm |
Cardiac pacemaker rate | ~100 / min |
Cardiac action potential | ~200 ms |
Cardiac phase 2 | ≥ 100 ms |
Cardiac resting potential | −90 mV |
Cardiac peak | ~+20 mV |
Cardiac twitch | ~400 ms |
Skeletal twitch | 10–100 ms |
Smooth twitch | ~5 s |
Cardiac Ca²⁺ from influx | ~20% |
Cardiac Ca²⁺ from SR | ~80% |
Removal via SERCA | ~70% |
Removal via NCX | ~28% |
Removal via PMCA | ~2% |
Distinctions that get mixed up¶
Pair | How to keep them apart |
|---|---|
Troponin vs calmodulin | Troponin sits on the thin filament in skeletal and cardiac muscle. Calmodulin floats free in smooth muscle and acts on the thick filament. Thin filament regulation vs thick filament regulation. |
Caveolae vs T tubules | Caveolae are shallow indentations in smooth muscle holding receptors and channels. T tubules are deep invaginations in skeletal and cardiac muscle carrying the action potential inward. |
Triad vs dyad | Two SR patches plus one T tubule in skeletal muscle. One SR patch plus one T tubule in cardiac. Count the structures. |
Phasic vs tonic | Phasic rests by default and contracts when needed, like the esophagus. Tonic contracts by default and relaxes when needed, like a sphincter. |
Single-unit vs multi-unit | Gap junctions and synchrony vs independence and dense innervation. Most smooth muscle is single-unit; ocular is the classic multi-unit case. |
MLCK vs MLCP | Kinase adds phosphate and activates myosin, the gas. Phosphatase removes it and deactivates, the brake. |
Gq vs Gi vs Gs | Gq raises IP₃. Gi inhibits cyclic AMP. Gs stimulates cyclic AMP. In smooth muscle, more cyclic AMP means less force. |
M₂ vs M₃ receptors | Both muscarinic, both bind acetylcholine. M₃ on smooth muscle uses Gq. M₂ on cardiac muscle lowers cyclic AMP. |
Alpha-1 vs alpha-2 vs beta-1 vs beta-2 | All bind norepinephrine. Alpha-1 raises IP₃ in vascular smooth muscle. Alpha-2 lowers cyclic AMP. Beta-1 is the cardiac receptor. Beta-2 raises cyclic AMP in skeletal muscle vasculature, relaxing it. |
Cyclic AMP in smooth vs cardiac muscle | Opposite effects. In smooth muscle it inhibits MLCK, reducing force. In cardiac muscle it raises PKA, increasing force. |
Skeletal vs cardiac length-tension | Same curve shape, different proposed mechanism. Skeletal is filament overlap. Cardiac is filament proximity raising calcium sensitivity, and gets its own name. |
What shifts the force-velocity curve | Fiber type in skeletal muscle. Myosin phosphorylation in smooth muscle. Stretch, or preload, in cardiac muscle. |
Can it be tetanized | Skeletal yes, smooth yes, cardiac no. Tetanizing the heart stops it. |
Check yourself¶
Try each question before opening the answer.
Solution to Exercise 1
(1) Stimulus raises free Ca2+; (2) Ca2+ binds a regulatory protein; (3) more cross-bridging and tension; (4) stimulus ends, Ca2+ falls and dissociates; (5) less cross-bridging, relaxation. Skeletal: SR release via DHPR/RyR, troponin C, SERCA. Cardiac: influx plus CICR, troponin C, SERCA/NCX/PMCA. Smooth: influx with CICR or IP3, calmodulin and MLCK, SERCA/NCX/PMCA and MLCP. (M4 slides 10, 31)
Solution to Exercise 2
Spindle rather than cylindrical; 5–10 µm thick rather than about 100; 30–200 µm long rather than up to 30 cm; no striations or sarcomeres; dense bodies rather than Z discs; less, scattered SR; no troponin; caveolae rather than T tubules; involuntary rather than voluntary. (M4 slide 2)
Solution to Exercise 3
Its thin filaments anchor to dense bodies scattered through the cell, with thick filaments between them, rather than to Z discs in repeating sarcomeres. With no repeating bands there is nothing to make stripes. (M4 slide 2)
Solution to Exercise 4
Phasic: the esophagus, relaxed at baseline and contracting when food is swallowed. Tonic: a sphincter or vascular smooth muscle, contracted at baseline and relaxing when needed. (M4 slide 4)
Solution to Exercise 5
Single-unit cells are joined by gap junctions. The few stimulated cells depolarize, positive ions flow through the gap junctions into neighbors, and the whole sheet depolarizes and contracts as one unit. (M4 slides 5, 7)
Solution to Exercise 6
Multi-unit cells are not electrically coupled, so each needs its own neural input. In return the nervous system can choose exactly how many cells contract, giving fine, graded control, as in the eye. (M4 slide 5)
Solution to Exercise 7
Sympathetic: most vascular contracts (vessels in exercising muscle relax); ocular, some contract and some relax to dilate the pupil; respiratory relaxes; GI and urinary relax. Parasympathetic: some vascular relaxes; ocular acts to constrict the pupil; respiratory contracts; GI and urinary contract. (M4 slide 6)
Solution to Exercise 8
The circular layer contracts and narrows the tube; the longitudinal layer contracts and shortens it. Alternating between them pushes contents along the digestive tract. (M4 slide 7)
Solution to Exercise 9
Ca2+ is positive like Na+, and its inward electrochemical gradient is very strong. Opening voltage-gated Ca2+ channels brings positive charge in fast, which depolarizes the membrane just as Na+ would. (M4 slide 11)
Solution to Exercise 10
Slow waves that spike at threshold (force follows the spikes); pacemaker potentials, automaticity (regular rhythmic force); summed action potentials (summed force); subthreshold shifts (force rises as Vm becomes less negative, falls as it becomes more negative). Force can also change with no voltage change, from ligands alone. (M4 slide 11)
Solution to Exercise 11
Electrical: depolarization → voltage-gated Ca2+ channels in caveolae → Ca2+ in → Ca2+ binds RyR → SR release (CICR). Ligand: agonist → GPCR (Gq) → phospholipase C → DAG + IP3 → IP3 receptor on SR → Ca2+ release. (M4 slide 12)
Solution to Exercise 12
Extracellular Ca2+ entering the cell binds the ryanodine receptor and opens it, releasing stored Ca2+ from the SR. The ligand is Ca2+ itself; the channel is the RyR, acting as a ligand-gated channel. (M4 slides 12, 33)
Solution to Exercise 13
Ca2+ binds calmodulin → Ca2+-calmodulin activates myosin light-chain kinase → MLCK phosphorylates the myosin light chain on the head → activated myosin binds actin → cross-bridge cycling and power stroke. (M4 slides 13–14)
Solution to Exercise 14
SERCA (into the SR) does most; the Na+-Ca2+ exchanger (out of the cell) is second; the plasma membrane Ca2+ ATPase is small. (M4 slide 15)
Solution to Exercise 15
MLCP works all the time. When Ca2+ falls, calmodulin releases it and MLCK shuts off, so the phosphatase works unopposed and myosin becomes dephosphorylated. Removing the gas is enough to stop the car. (M4 slide 16)
Solution to Exercise 16
More force: raise IP3 (Gq: ACh on M3, NE on alpha-1); lower cAMP (Gi: NE on alpha-2); inhibit MLCP through rho kinase. Less force: raise cAMP (Gs: NE on beta-2), which inhibits MLCK; raise cGMP (nitric oxide), which raises MLCP. (M4 slides 20–21)
Solution to Exercise 17
Nitric oxide is a powerful smooth muscle relaxant vital to vascular health. Losing its production in blood vessels is the first sign of vascular dysfunction that leads to hypertension, coronary artery disease, heart attack, and stroke. (M4 slide 21)
Solution to Exercise 18
Sensitization: less Ca2+ gives the same contraction, the curve shifts left (low MLCP). Desensitization: more Ca2+ is needed, the curve shifts right (high MLCP). (M4 slide 22)
Solution to Exercise 19
Outside in: pericardium about 1 mm, myocardium up to 9 mm, endocardium about 0.5 µm. (M4 slide 25)
Solution to Exercise 20
Shared with skeletal: troponin, T tubules, sarcomeres. Shared with smooth: automaticity, autonomic innervation, gap junctions, long twitch duration. (M4 slides 27–28)
Solution to Exercise 21
The heart must beat continuously with no neural command, so pacemaker cells must start every beat; without automaticity there is no heartbeat. Smooth muscle can be driven by nerves, hormones, stretch, or local chemicals, so pacemaker cells are needed only in some places, such as the intestines. (M4 slide 28)
Solution to Exercise 22
0 upstroke: Na+ in. 1 transient repolarization: a little K+ out. 2 plateau: K+ out balanced by Ca2+ in. 3 delayed repolarization: Ca2+ channels close, K+ out continues. 4 rest: Na+-K+ pump. (M4 slide 32)
Solution to Exercise 23
Positive charge leaves as K+ at about the rate it enters as Ca2+, so Vm holds still for 100 ms or more. The Ca2+ entering during the plateau triggers CICR and drives contraction. (M4 slide 32)
Solution to Exercise 24
About 20% enters from the extracellular fluid through voltage-gated Ca2+ channels during phase 2. That Ca2+ binds the RyR and triggers release of the other 80% from the SR: calcium-induced calcium release. (M4 slide 33)
Solution to Exercise 25
Resting cell stretch is proportional to active force. Proposed mechanism: stretch → filaments closer together → greater Ca2+ sensitivity → more force. Skeletal length-tension depends on filament overlap; cardiac appears to depend on filament proximity. (M4 slide 37)
Solution to Exercise 26
Voltage-gated Ca2+ channel (more influx) and RyR (more release) raise contraction. Phospholamban (switched off, freeing SERCA) and troponin I (Ca2+ leaves troponin C faster) speed relaxation. (M4 slide 40)
Solution to Exercise 27
Phospholamban brakes SERCA. Phosphorylation turns phospholamban off, so the brake comes off and SERCA pumps Ca2+ back into the SR faster and more completely. Inhibiting an inhibitor speeds the process. (M4 slide 40)
Solution to Exercise 28
ACh on M2 lowers cAMP and PKA, the reverse of sympathetic. Less phosphorylation of the Ca2+ channel and RyR gives weaker contraction; less phosphorylation of phospholamban and troponin I gives slower relaxation. The effects are weak. (M4 slide 41)
Solution to Exercise 29
Skeletal 10–100 ms: fast reflexes and movement. Cardiac about 400 ms: long enough to eject blood, short enough to relax and refill. Smooth about 5 s: holds organ walls contracted for long periods. (M4 slide 45)
Solution to Exercise 30
A tetanized heart would not relax, and a heart that cannot relax cannot refill: it has stopped. Cardiac muscle relies almost entirely on oxidative ATP, making it highly fatigue resistant, which it must be because it can never rest. (M4 slide 47)