Membrane Potentials
Usually weeks 2-3 of a medical physiology courseThis is the most conceptually loaded stretch of the course, and the one worth over-studying: everything electrical for the rest of the year — nerve, skeletal muscle, cardiac conduction, the EKG — is built from what happens here. The exam asks it three ways: predict a potential from a concentration change (Nernst thinking), name the channel state behind each phase of the action potential, and reason about what a drug or an electrolyte disorder does to excitability. Learn the K+ story first — the resting membrane is mostly a K+ electrode — and the rest is corrections to it.
This guide is the frame. The exams are written from your lectures— drop this unit's slides on the dashboard to get flashcards and board-style questions from your own course, and quiz them all semester (a course whose exams re-test earlier units rewards nothing more than early, repeated self-testing). The physiology playbook has the weekly loop.
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AI-authored study notes, not faculty-reviewed and not medical advice. Verify every mechanism against your course materials and faculty; programs differ in emphasis.
High-Yield Pearl
Every membrane-potential question is 'which ion's channels are open, and toward which equilibrium potential is the membrane being pulled?' — answer that and depolarize-vs-hyperpolarize, every AP phase, and both K+ emergencies fall out for free.
What the exam asks
Mechanisms, curves, and what happens when each one fails.
- Why there is a resting potential at all. Two ingredients: concentration gradients (the Na+/K+-ATPase keeps K+ high inside, Na+ high outside) and selective permeability (at rest the membrane leaks K+ far better than Na+). K+ diffuses out down its gradient, leaving unbalanced negative charge behind, until the electrical pull back in balances the chemical push out. The result sits near −70 mV in a typical neuron — close to K+'s equilibrium potential, because K+ has the most open channels at rest.
- The Nernst (equilibrium) potential. For one ion, the membrane potential at which electrical and chemical forces balance exactly — no net flux. Approximate values worth memorizing: EK ≈ −90 mV, ENa ≈ +60 mV, ECa ≈ +120 mV, ECl ≈ −70 mV. Two rules do most exam work: the membrane potential is always pulled TOWARD the equilibrium potential of whichever ion is most permeant, and changing an ion's concentration gradient moves its equilibrium potential (raise extracellular K+ and EK becomes less negative — the cell depolarizes).
- Resting potential is a weighted average (the chord conductance idea). The actual resting potential is a permeability-weighted compromise among the permeant ions — mostly K+ at rest, which is why Vm (−70) sits near EK (−90) but not on it: a small resting Na+ leak drags it positive. The Na+/K+-ATPase contributes a few millivolts directly (3-for-2 is electrogenic) but its real job is maintaining the gradients. When a question opens a channel, ask 'toward which equilibrium potential does the membrane now move?' — that one move answers depolarize-or-hyperpolarize for any ion.
- Graded potentials vs action potentials. Graded potentials (synaptic, receptor, pacemaker) are local, decremental (they decay with distance), scale with stimulus size, and can summate. Action potentials are all-or-none, self-propagating without decrement, and cannot summate — stimulus intensity is coded by FREQUENCY, not amplitude. Graded potentials are the input arithmetic; the axon hillock's threshold decides whether the axon fires.
- The action potential, phase by phase. At threshold (~−55 mV), voltage-gated Na+ channels open — Na+ entry depolarizes, opening more Na+ channels (positive feedback) and driving Vm toward ENa (+60, overshooting 0). Na+ channels then INACTIVATE (a time-dependent gate, not mere closure) while slower voltage-gated K+ channels open; K+ efflux repolarizes. K+ channels close slowly, so the potential undershoots toward EK — the afterhyperpolarization — before leak channels restore rest. The pump did not do the repolarizing; it rebuilds gradients over the long run.
- The two gates of the Na+ channel and the refractory periods. The Na+ channel has an activation gate (opens fast on depolarization) and an inactivation gate (closes slowly on depolarization, reopens only after repolarization). ABSOLUTE refractory period: inactivation gates closed — no stimulus of any size can fire a second AP; this caps firing frequency and forbids summation. RELATIVE refractory period: enough channels have recovered that a LARGER-than-normal stimulus can fire, against the afterhyperpolarization. Inactivation is also why sustained depolarization (high K+) ultimately SILENCES excitable tissue rather than exciting it.
- Conduction velocity — diameter and myelin. Velocity rises with axon diameter (less internal resistance) and with myelination (the sheath raises membrane resistance and lowers capacitance, so current spreads farther before leaking out). In myelinated axons the AP regenerates only at the nodes of Ranvier — saltatory conduction. Large myelinated Aα fibers (motor, proprioception) conduct fastest; small unmyelinated C fibers (slow pain, temperature) slowest — the reason sharp pain arrives before the burn.
- Extracellular ions set excitability. K+ sets the resting potential: hyperkalemia depolarizes (less negative EK) — transiently excitable, then Na+-channel inactivation silences the tissue; hypokalemia hyperpolarizes, moving rest away from threshold. Ca2+ sets the threshold's effective position by screening membrane charge: hypocalcemia makes Na+ channels open more easily (spontaneous firing — tetany, Chvostek and Trousseau signs); hypercalcemia stabilizes the membrane (lethargy, weakness). Keep the two axes separate: K+ moves REST, Ca2+ moves the effective THRESHOLD.
- Where the numbers touch the heart. The same channel logic runs cardiac muscle with different casting: fast Na+ channels for the upstroke in working myocardium, L-type Ca2+ channels sustaining the plateau, and inward-rectifier K+ channels holding rest. This is why plasma K+ disorders show up first on an EKG, and why class I antiarrhythmics (Na+-channel blockers) and local anesthetics share a mechanism — use-dependent Na+-channel blockade. The full cardiac action potentials get their own unit; the grammar is this week's.
Worth drilling · 25 concepts
Each with the one fact that identifies it. Your course's slides are the authority; use this to check your list against.
- 1Resting membrane potential — about −70 mV; set mainly by K+ permeability and the K+ gradient
- 2Nernst equilibrium potential — the voltage at which one ion's electrical and chemical forces balance
- 3EK ≈ −90 mV — potassium's equilibrium potential; rest sits near it because K+ leaks most
- 4ENa ≈ +60 mV — sodium's equilibrium potential; the AP upstroke heads toward it
- 5Chord conductance idea — Vm is a permeability-weighted average of the permeant ions' equilibrium potentials
- 6Na+/K+-ATPase (electrogenic) — 3-for-2 exchange adds a few negative millivolts; mainly maintains the gradients
- 7Graded potential — local, decremental, scales with stimulus, summates
- 8Action potential — all-or-none, propagates without decrement; intensity coded by frequency
- 9Threshold — about −55 mV; where Na+ entry becomes self-regenerating
- 10AP upstroke — voltage-gated Na+ channels open; positive feedback toward ENa
- 11Na+ channel inactivation gate — closes with sustained depolarization; reopens only after repolarization
- 12Repolarization — delayed voltage-gated K+ channels open while Na+ channels inactivate
- 13Afterhyperpolarization — slow-closing K+ channels drag Vm toward EK below rest
- 14Absolute refractory period — Na+ inactivation gates closed; no second AP at any stimulus size
- 15Relative refractory period — partial recovery; a larger-than-normal stimulus can fire
- 16Saltatory conduction — AP regenerates node to node in myelinated axons; fastest conduction
- 17Node of Ranvier — myelin gap dense with voltage-gated Na+ channels
- 18Myelin — raises membrane resistance, lowers capacitance; current spreads farther per node
- 19C fibers — small, unmyelinated, slowest: slow burning pain and temperature
- 20Hyperkalemia — depolarizes rest toward threshold, then inactivation silences the tissue
- 21Hypokalemia — hyperpolarizes rest away from threshold; weakness and arrhythmia
- 22Hypocalcemia — Na+ channels open more easily; tetany, Chvostek and Trousseau signs
- 23Hypercalcemia — stabilizes the membrane; lethargy, weakness, constipation
- 24Local anesthetics — use-dependent block of voltage-gated Na+ channels; small pain fibers first
- 25Tetrodotoxin — blocks the voltage-gated Na+ channel; no upstroke, no AP
Practice it
Active recall over the drill list — flip and claim, match the pairs, produce the answers cold, fill in the diagram, or read the curves like the exam does.
Every concept on the drill list, one card at a time — the name up front, the fact that identifies it on the flip. Claim each card honestly and the deck learns what to lead with next time. Progress lives in this browser only.
What everyone misses
The distinctions that lose points on this material, year after year.
- Hyperkalemia does not make tissue permanently MORE excitable. The half-learned version — 'depolarized = closer to threshold = excitable' — is only act one. Sustained depolarization closes Na+-channel inactivation gates that can't reopen without repolarization, so severe hyperkalemia ends in INEXCITABLE muscle and heart (flaccid weakness, sine-wave EKG). The exam's favorite version asks why high K+ eventually causes paralysis rather than seizures of activity.
- Repolarization is K+ efflux, not the pump. The Na+/K+-ATPase is the intuitive hero, but the millisecond-scale repolarization is delayed K+ channels opening (plus Na+ inactivation). The pump restores the gradients over seconds to minutes and contributes only a few steady millivolts. An answer choice crediting the pump with ending the action potential is the trap.
- The equilibrium potential moves; the resting potential follows only if the ion is permeant. Change extracellular K+ and EK moves — and Vm follows, because the resting membrane is K+-selective. Change extracellular Na+ and ENa moves — but resting Vm barely budges (Na+ permeability at rest is tiny); what changes is the height of the AP overshoot. Match the concentration change to the moment that ion's channels are open.
- Ca2+ acts on threshold, K+ acts on rest. Students blend the electrolyte effects into one 'excitability' blur. Keep the axes apart: K+ disorders move the RESTING potential (hyper- depolarizes, hypo- hyperpolarizes); Ca2+ disorders move the effective THRESHOLD by screening the membrane (hypo- brings threshold effectively closer — tetany; hyper- pushes it away — lethargy). A vignette of perioral tingling and carpal spasm is a threshold story, not a resting-potential story.
- All-or-none does not mean all APs look identical everywhere. All-or-none means amplitude doesn't scale with stimulus IN A GIVEN CELL — a bigger stimulus gives more frequent APs, not taller ones. Between cell types, AP shape varies enormously (a ventricular myocyte's plateau vs a neuron's spike). 'How does the nervous system code intensity?' — frequency, plus recruitment of more fibers — is the direct form of this question.
- Myelin speeds conduction by insulating, not by conducting. The sheath doesn't carry current — it stops current from LEAKING, so the depolarization spreads farther down the axon core before needing regeneration at a node. That's why demyelination doesn't just slow conduction; when current leaks below threshold before reaching the next node, conduction FAILS outright — the physiology behind multiple sclerosis symptoms.
Clinical correlations
Where this unit shows up again — in clinic, on rotations, and on the boards.
- Hyperkalemia on the EKG. Rising K+ depolarizes cardiac cells and speeds repolarization: peaked T waves first, then widening QRS as depolarized fibers conduct slowly (inactivated Na+ channels), ending in a sine-wave pattern and arrest. IV calcium 'stabilizes the membrane' — it restores the threshold-to-rest separation without changing K+ at all: pure week-three physiology as a life-saving order.
- Hypocalcemic tetany. Post-thyroidectomy perioral numbness, carpopedal spasm, Chvostek and Trousseau signs: low ionized Ca2+ lets voltage-gated Na+ channels open at smaller depolarizations, so nerves fire spontaneously. Hyperventilation reproduces it by alkalosis — more Ca2+ binds albumin, ionized Ca2+ falls — same mechanism, normal total calcium.
- Local anesthetics. Lidocaine and its relatives block voltage-gated Na+ channels — preferentially in their open/inactivated states, so rapidly firing fibers are blocked first (use-dependence). Small-diameter fibers succumb before large ones: pain and temperature go before touch, and motor function last — the order every patient notices as the dentist's block sets in.
- Multiple sclerosis and demyelination. Loss of central myelin slows saltatory conduction or blocks it entirely when leaking current can't bring the next node to threshold — relapsing deficits (optic neuritis, weakness, sensory loss). Conduction worsens with heat (Uhthoff phenomenon) because warm channels inactivate faster, shaving the safety margin. Guillain-Barré is the peripheral twin.
- Tetrodotoxin and the channel toxins. Pufferfish TTX plugs voltage-gated Na+ channels from outside: no upstroke, no AP, flaccid paralysis with an intact mind. The channel toxins bracket the mechanism from both sides — TTX blocks the channel; ciguatoxin holds it open. If you can predict each toxin's effect from the channel's job, this material has stuck.
- Periodic paralyses — the channelopathy vignettes. Episodic flaccid weakness after exercise or a carbohydrate load with a K+ shift: hypokalemic periodic paralysis (K+ driven into cells, rest hyperpolarizes) and its hyperkalemic twin (channel mutations letting depolarization inactivate Na+ channels). Rare diseases, but standard exam fodder because they test the resting-potential logic in both directions.
- Class I antiarrhythmics. Quinidine, lidocaine, flecainide — Na+-channel blockers whose use-dependence makes them selective for fast-firing (tachycardic or ectopic) tissue over normal rhythm. The subclasses differ in how fast they let go of the channel. The full pharmacology comes later; the receptor is this unit's channel.