Anaes · Applied cardiovascular & respiratory physiology

Cell membrane & action potential

Also known as Membrane potential · Action potential · Resting membrane potential · Nernst equation · Goldman equation · Sodium-potassium pump

Excitable cells — nerve, skeletal and cardiac muscle — generate and conduct electrical signals because ion concentrations differ across the lipid bilayer and the membrane is selectively permeable. The framework rests on five exam-critical ideas: the resting membrane potential (around minus 70 millivolts in nerve) is set chiefly by the outward leak of potassium, formalised by the Nernst equation for a single ion and the Goldman-Hodgkin-Katz equation for the mixed-ion reality; the sodium-potassium ATPase is an electrogenic pump that maintains the gradients against the leak; the action potential is an all-or-nothing, regenerative reversal of the membrane potential driven by voltage-gated sodium inflow then potassium outflow; conduction velocity is determined by axon diameter and myelination (saltatory conduction); and the whole system is the molecular target of anaesthetic drugs — local anaesthetics block the voltage-gated sodium channel, general anaesthetics modulate ligand-gated channels, and inherited channel defects (channelopathies) cause disease. Built on the Goldman-equation analysis (Silverstein 2025), the sodium-gradient and membrane-potential work (Nicholls 2024), the Na,K-ATPase FXYD-regulator review (Li 2026), the voltage-gated sodium-channel structural review (Kuznetsov 2025), the neuronal electrical-activity model (Rafati 2025), the cardiac ion-channel cardiotoxicity review (Orts 2026), the sudden-cardiac-death genetics review (Lovric Bencic 2025), and the local-anaesthetic-resistance review (Kanchetty 2026).

high8 referencesUpdated 26 July 20266 min readVerification in progress

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The resting membrane potential is dominated by potassium permeability, not sodium — hyperkalaemia depolarises the cell (less negative), which inactivates sodium channels and initially reduces then abolishes excitability, the mechanism of the ECG changes and asystole in severe hyperkalaemia.
Local anaesthetics block the voltage-gated sodium channel from the inside of the membrane, binding preferentially to the open and inactivated states (use-dependent block) — this is why a nerve that is firing repeatedly is blocked more than a quiescent one, and why inflamed, acidic tissue (ionised drug trapped outside) resists blockade.
The action potential is all-or-nothing: a stimulus that reaches threshold generates a full response, and conduction is non-decremental. A sub-threshold local response decays with distance — the basis of the refractory period and unidirectional propagation.
The absolute refractory period (during depolarisation and early repolarisation, while sodium channels are inactivated) prevents summation and tetany in cardiac muscle and sets a ceiling on heart rate; loss of normal refractoriness underlies re-entrant arrhythmia.
Channelopathies — inherited defects of ion-channel genes such as SCN5A (the cardiac sodium channel) — cause the long-QT and Brugada syndromes: structurally normal hearts with a high risk of sudden arrhythmic death, and an obvious reason why anaesthetists must understand ion-channel physiology.

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Practise this topic8 MCQs with explanations

Target exams

ANZCAFRCAABAEDAICFCAIFCA_SA

Red flags

The resting membrane potential is dominated by potassium permeability, not sodium — hyperkalaemia depolarises the cell (less negative), which inactivates sodium channels and initially reduces then abolishes excitability, the mechanism of the ECG changes and asystole in severe hyperkalaemia.
Local anaesthetics block the voltage-gated sodium channel from the inside of the membrane, binding preferentially to the open and inactivated states (use-dependent block) — this is why a nerve that is firing repeatedly is blocked more than a quiescent one, and why inflamed, acidic tissue (ionised drug trapped outside) resists blockade.
The action potential is all-or-nothing: a stimulus that reaches threshold generates a full response, and conduction is non-decremental. A sub-threshold local response decays with distance — the basis of the refractory period and unidirectional propagation.
The absolute refractory period (during depolarisation and early repolarisation, while sodium channels are inactivated) prevents summation and tetany in cardiac muscle and sets a ceiling on heart rate; loss of normal refractoriness underlies re-entrant arrhythmia.
Channelopathies — inherited defects of ion-channel genes such as SCN5A (the cardiac sodium channel) — cause the long-QT and Brugada syndromes: structurally normal hearts with a high risk of sudden arrhythmic death, and an obvious reason why anaesthetists must understand ion-channel physiology.

Meet the patient

A 62-year-old with end-stage renal failure presents for emergency laparotomy. Potassium is 7.1 mmol per litre. The ECG shows a sine wave — no P waves, no discrete QRS, just one broad oscillation. The trainee asks: should high potassium not make the heart more excitable?^[7]

It does, for about thirty seconds. Then the depolarised membrane inactivates the sodium channels and the heart stops conducting. The same physics explains why your lidocaine barely works in an acidic abscess. This is membrane physiology that kills at the molecular level.^[7]^[8]

References8Show

[1]Silverstein TP. Explaining neuronal membrane potentials: The Goldman equation vs. Lee's TELC hypothesis Neuroscience, 2025.PMID 39755228
[2]Nicholls DG. Does a transmembrane sodium gradient control membrane potential in mammalian mitochondria? Cell Calcium, 2024.PMID 39488142
[3]Li X, et al. The functions of FXYD family members in human health and disease Genes Dis, 2026.PMID 41630949
[4]Kuznetsov VG, et al. Voltage-Gated Sodium Channel Substitutions Underlying Tetrodotoxin Resistance in Nemerteans: Ecological and Evolutionary Implications Int J Mol Sci, 2025.PMID 41465217
[5]Rafati AH, et al. A Model-Based Approach to Neuronal Electrical Activity and Spatial Organization Through the Neuronal Actin Cytoskeleton Methods Protoc, 2025.PMID 40700314
[6]Orts DJB, et al. Chemically induced cardiotoxicity: Role of voltage dependent ion channels Curr Top Membr, 2026.PMID 42082304
[7]Lovrić Benčić M, Levicki R Genetics of Sudden Cardiac Death Diseases, 2025.PMID 41590224
[8]Kanchetty N. Local Anesthetic Resistance: Pathophysiology, Clinical Recognition, and Management Strategies Curr Pain Headache Rep, 2026.PMID 41995765