Evidence-based physiotherapy and rehabilitation resources
Editorial & review policy
Evidence-based physiotherapy and rehabilitation resources
Editorial & review policyHuman Physiology · Foundations
Every nerve impulse, every contraction, every breath of oxygen that reaches a muscle depends on something crossing a membrane. This page explains the five ways it happens, and which ones cost energy.
Part 1 · Foundations · Chapter 3 of 47
By the end of this page you should be able to:
The membrane is a barrier, and the cell has to get things through it. Oxygen, glucose and ions all need to cross, and so does water.
Physiotherapy touches this constantly. Electrotherapy works on membranes that move ions. Exercise improves blood glucose because contracting muscle opens its own route for glucose. Fatigue in a patient with heart failure is partly a failure of ion pumping.
Learn the five mechanisms here once, and the nerve impulse, the kidney and the gut later in this subject become applications rather than new topics.
Substances move by two broad means. Passive transport needs no energy from the cell. Substances move down their concentration gradient, from high to low, like water flowing downhill.
Active transport uses energy to move substances against their gradient, uphill. The energy comes either directly from ATP (primary active) or from a gradient that ATP has already built (secondary active).
Figure 1 · Five ways across the membrane
| Mechanism | Energy | Protein needed? | Saturates? | Example |
|---|---|---|---|---|
| Simple diffusion | None | No | No | O₂ and CO₂ across the lung and tissue capillaries |
| Channel-mediated diffusion | None | Channel | Practically no | Na⁺ entry during the nerve impulse |
| Carrier-mediated (facilitated) diffusion | None | Carrier | Yes | Glucose entering muscle through GLUT4 |
| Primary active transport | ATP, directly | Pump | Yes | Na⁺–K⁺ pump; calcium pump of the sarcoplasmic reticulum |
| Secondary active transport | Na⁺ gradient made by ATP | Co-transporter or exchanger | Yes | Na⁺–glucose uptake in gut and kidney |
| Vesicular transport | ATP | Membrane machinery | — | Release of acetylcholine at the neuromuscular junction |
Molecules are in constant random motion. Where there are more of them, more move away than move in, so the net flow runs from high concentration to low until the two sides are equal. That net flow is diffusion.
Fick’s law says the rate of diffusion across a barrier rises with the surface area, the concentration difference and the permeability of the barrier. It falls as the barrier gets thicker.
Fick’s law in words
Rate of diffusion ∝ (surface area × concentration difference × permeability) ÷ thickness of the barrier.
Each term has a clinical face. Lung surface area is lost in emphysema. The gradient for oxygen falls at altitude. The barrier thickens in pulmonary fibrosis, and the distance from capillary to cell grows when tissue is oedematous.
Diffusion is fast over very short distances and very slow over long ones. The time taken rises with the square of the distance. That is why cells sit within a few cell-widths of a capillary, and why swelling can starve tissue of oxygen.
Ions and large water-soluble molecules cannot cross the lipid core. They need proteins.
Channels are pores that let particular ions through very quickly. Most are gated: they open in response to a voltage change, a chemical signal or mechanical stretch. Voltage-gated sodium channels produce the nerve impulse; stretch-gated channels help mechanoreceptors sense movement.
Carriers bind a molecule, change shape and release it on the other side. Because each carrier can handle only so many molecules each second, carrier transport has a maximum rate.
Figure 2 · Why carriers saturate
Glucose enters muscle through a carrier called GLUT4. At rest most GLUT4 sits inside the fibre in storage vesicles. Insulin brings it to the surface, and so does muscle contraction, by its own separate signalling pathway [4].
This is why exercise lowers blood glucose even when insulin is not working well, and why it matters so much in type 2 diabetes. Training also increases the total amount of GLUT4 in muscle, more than any other stimulus [4].
Osmosis is the movement of water across a membrane towards the side with more dissolved particles that cannot cross. Water moves through the lipid itself and, much faster, through water channels called aquaporins. Agre’s discovery of aquaporins earned the 2003 Nobel Prize in Chemistry [3].
Osmolality is the number of dissolved particles per kilogram of water. Body fluids sit at about 275–295 mOsm/kg, and the ICF and ECF are kept at the same osmolality, so water does not shift between them at rest.
Tonicity describes what a solution does to cell volume. It depends only on particles that cannot cross the membrane.
Figure 3 · Osmosis and tonicity
| Solution | Tonicity | Effect on cells | Clinical note |
|---|---|---|---|
| 0.9% sodium chloride (normal saline) | Isotonic | No change in volume | Expands the ECF; stays mostly outside cells |
| 5% dextrose | Isotonic in the bag, hypotonic in effect | Glucose is taken up, leaving free water that enters cells | Not used to restore circulating volume |
| Pure water | Hypotonic | Cells swell and may burst | Never given intravenously |
| 3% sodium chloride | Hypertonic | Cells shrink | Used under close monitoring, for example to reduce brain swelling |
The most important pump in the body was found in nerve by Jens Skou in 1957. He described an enzyme in nerve membranes that split ATP only when both sodium and potassium were present [1]. It is the Na⁺–K⁺ ATPase, the sodium–potassium pump.
Figure 4 · The sodium–potassium pump
Each cycle moves three sodium ions out and two potassium ions in, using one ATP. The result is the chemical difference between the two compartments: potassium high inside, sodium high outside. Because more positive charge leaves than enters, the pump also adds slightly to the negative charge inside the cell.
These gradients are stored energy. A nerve impulse spends them as sodium rushes in and potassium leaks out. Secondary active transport spends the sodium gradient to move other substances. The pump then restores them.
Clausen’s review shows how this matters during exercise. Each impulse in a working muscle lets sodium in and potassium out. Unless pumps restore the gradients, excitability fails. Contraction can switch on up to all available pumps within about ten seconds [2].
Pump numbers also adapt. Training increases the number of pumps in muscle. Immobilisation, heart failure, hypothyroidism and diabetes reduce it, and the loss may contribute to the fatigue seen in those conditions [2].
Other pumps work in the same way. The calcium pump of the sarcoplasmic reticulum pulls calcium back after each contraction so that muscle can relax. The proton pump of the stomach makes acid.
Secondary active transport uses the sodium gradient as an energy source. A co-transporter (symporter) carries sodium and another substance in the same direction. An exchanger (antiporter) moves them in opposite directions.
The sodium–glucose co-transporter SGLT1 in the gut is the classic example. Sodium flows into the cell down its gradient and drags glucose in with it, even when glucose inside is already high.
Figure 5 · Secondary active transport in the gut
In cholera, a toxin makes the gut secrete huge volumes of salt and water. Researchers found that the sodium–glucose co-transport still works in these patients [5]. Giving salt and glucose together by mouth therefore drives sodium, and the water that follows it, back into the body.
That insight produced oral rehydration therapy, one of the most important medical advances of the twentieth century. It has saved millions of lives from dehydrating diarrhoea [5].
Other examples include the sodium–calcium exchanger in heart muscle, which removes calcium after each beat, and the co-transporters in the kidney tubule.
| Process | What happens | Example |
|---|---|---|
| Exocytosis | A vesicle fuses with the membrane and releases its contents outside | Acetylcholine release at the neuromuscular junction; hormone secretion |
| Endocytosis | The membrane folds in and pinches off a vesicle containing fluid or particles | Uptake of cholesterol-carrying particles |
| Receptor-mediated endocytosis | Specific molecules bind receptors, then are taken in | Iron uptake bound to its transport protein |
| Phagocytosis | Large particles are engulfed | Macrophages clearing debris after a muscle injury |
| Transcytosis | Material crosses a cell by endocytosis on one side and exocytosis on the other | Antibodies crossing the placenta |
| Situation | Transport principle | What you do |
|---|---|---|
| Diabetic patient before exercise | Contraction increases glucose uptake | Check blood glucose before and after; carry fast-acting glucose |
| Swollen post-operative limb | Longer diffusion distance | Elevation, movement and compression to reduce oedema |
| Long session in heat | Sweat loses salt and water | Plan fluid with salt; watch for cramps and dizziness |
| Patient on digoxin or diuretics | Drugs acting on pumps and transporters | Watch heart rate response and potassium results |
Practical skill · reading an electrolyte report
Before a demanding session with a renal, cardiac or diabetic patient, look at the most recent sodium, potassium and glucose results. Values outside the normal range are not your diagnosis to make, but they are a reason to check with the medical team before loading the patient.
Classify the mechanisms of transport across the cell membrane. Describe the sodium–potassium pump in detail.
The pump is taught as a fixed housekeeping enzyme that keeps the resting gradients, and glucose uptake into muscle is taught as an insulin-dependent process.
The pump is a regulated, trainable system. It is switched on within seconds by excitation, and its quantity in muscle rises with training and falls with disuse and chronic disease [2].
Contraction is a second, independent route to glucose uptake through GLUT4, and training is the strongest stimulus for building more transporters [4].
Membrane transport proteins are not fixed fittings. Like mitochondria, they adapt to how a tissue is used, which is part of why training changes fatigue and glucose control.
10 questions on this page. Tap one to see the answer and the reasoning.
Answer: (C) Small, uncharged, fat-soluble molecules such as oxygen dissolve in the lipid core; ions need channels or carriers [3].
Answer: (B) Saturation is the signature of a limited number of carriers, as with the glucose transporters [4].
Answer: (B) Three sodium out and two potassium in per cycle; the enzyme was first identified by Skou in nerve [1, 2].
Answer: (B) Skou described a sodium- and potassium-dependent ATPase in peripheral nerve in 1957 [1].
Answer: (A) Agre’s discovery of aquaporins explained how some membranes are far more permeable to water than lipid alone allows [3].
Answer: (C) Pure water is hypotonic, so water moves into the cell by osmosis, through lipid and aquaporins [3].
Answer: (B) Excitation can activate up to all available pumps within seconds; their capacity helps protect excitability and endurance [2].
Answer: (B) Training up-regulates pump content [2] and is the most potent stimulus for increasing muscle GLUT4 [4].
Answer: (B) Contraction translocates GLUT4 to the membrane and T-tubules through its own signalling pathway [4].
Answer: (B) The intact sodium–glucose co-transport in cholera was the discovery behind oral rehydration therapy [5].
Key takeaways
| Source | Why it earns its place |
|---|---|
| Hall JE, Hall ME — Guyton and Hall Textbook of Medical Physiology | Clear chapter on membrane transport and osmosis |
| Clausen T — Physiological Reviews, 2003 | The definitive review of the pump in working muscle [2] |
| Richter EA, Hargreaves M — Physiological Reviews, 2013 | How exercise drives muscle glucose uptake [4] |
| Agre P — Nobel Lecture, 2004 | A readable first-hand account of discovering water channels [3] |
Reviewed by the Physiotherapist India Team. · Human Physiology contents