2.1 Resting Membrane Potential and Cell Membrane Physiology
Key Takeaways
- Typical axonal resting membrane potential is about −70 to −90 mV (inside negative) because resting K+ permeability far exceeds Na+ permeability, so voltage sits near EK, not ENa.
- Standard teaching concentrations put Na+ high outside (~145 mmol/L) and K+ high inside (~140 mmol/L); reversing those sides is a classic physiology trap.
- A worked Nernst example with 4 mmol/L K+ outside and 140 mmol/L K+ inside gives EK ≈ 61 × log10(4/140) ≈ −94 mV; Goldman weighting then explains why rest is a little positive to EK.
- The Na+/K+ ATPase moves 3 Na+ out and 2 K+ in per ATP and maintains gradients; moment-to-moment rest is still set by open (mainly K+) channels, not by the pump as the only negative-charge source.
- SNAPs and CMAPs are extracellular fields from many axons leaving rest together; surface electrodes never read the intracellular −70 mV value itself.
2.1 Resting Membrane Potential and Cell Membrane Physiology
Nerve conduction studies (NCS) record sensory nerve action potentials (SNAPs) and compound muscle action potentials (CMAPs). Those traces are not intracellular voltmeter readings. They are extracellular fields created when many axons leave rest and depolarize together. If rest is vague, stimulation, threshold, and amplitude will feel like button-pushing rather than physiology. This OpenExamPrep chapter teaches the membrane starting point of every volume-conducted potential you mark on a screen.
The lipid bilayer and why ions need channels
The axonal cell membrane is a phospholipid bilayer: two sheets of lipid with hydrophobic fatty-acid tails packed inward and hydrophilic heads facing the watery axoplasm and extracellular fluid. Charged ions do not dissolve through that lipid core, so the bilayer behaves as an electrical insulator — a thin capacitor with very high resistance except where proteins pierce it. Ion channels are protein pores that open or close and give selected ions an aqueous path. Pumps are different: they consume metabolic energy to move ions against their gradients.
Three channel families matter for this domain. Leak channels (resting potassium channels are the prototype) stay open at negative voltages and set background permeability. Voltage-gated channels are mostly closed at rest and open when voltage changes; they generate the action potential (AP) in the next section. Ligand-gated channels open when a chemical transmitter binds; they dominate synapses and the neuromuscular junction more than the internodal axon under a stimulator cathode.
Because the bilayer separates charge, the axon holds a membrane potential: voltage of the inside relative to the outside. By convention the extracellular potential is treated as zero, so a resting membrane potential (RMP) of −70 to −90 millivolts (mV) means the axoplasm is 70 to 90 mV negative to the interstitial fluid. Teaching diagrams often mark −70 mV as a round number; large myelinated axons commonly rest closer to −80 to −90 mV. Both values sit in the range this physiology expects.
Intracellular versus extracellular ions (typical teaching values)
Ion identity is the highest-yield trap in basic membrane physiology. Sodium (Na+) is high outside and low inside. Potassium (K+) is high inside and low outside. Reverse that pair and every later story about depolarization and rest collapses.
| Ion | Typical intracellular concentration | Typical extracellular concentration | Chemical driving force at rest |
|---|---|---|---|
| Sodium (Na+) | about 15 mmol/L | about 145 mmol/L | strongly inward |
| Potassium (K+) | about 140 mmol/L | about 4 mmol/L (often taught as 4–5 mmol/L) | outward |
| Chloride (Cl−) | about 5–10 mmol/L | about 110 mmol/L | inward in many neurons |
| Calcium (Ca2+) | about 0.0001 mmol/L (100 nmol/L) | about 1–2 mmol/L | extremely inward |
| Organic anions (proteins, phosphates) | high | low | largely trapped inside; they do not cross the bilayer |
These numbers are standard neurophysiology teaching ranges, not a laboratory reference interval printed on a patient report and not a claim that every axon has identical millimolar values. They exist so you can reason about Nernst potentials and about why a little extra extracellular K+ is electrically dangerous.
Na+ wants to enter both because it is more concentrated outside and because the negative interior attracts cations. K+ wants to leave down its concentration gradient, but the negative interior pulls K+ back in. Equilibrium for one ion is the voltage at which those two forces cancel: the Nernst potential (equilibrium potential) for that ion.
Calcium is not the rest-setting ion in axons even though its chemical gradient is enormous. Resting Ca2+ permeability is tiny, so it barely weights the resting voltage. Calcium matters at terminals and muscle, not as the reason RMP is −70 mV. Chloride can stabilize voltage in cells with appreciable Cl− permeability, but the candidate's first pairing must remain: Na+ outside, K+ inside, K+ leak dominating rest.
Worked Nernst example for potassium
A simplified teaching form of the Nernst equation for a monovalent cation near body temperature is:
E_ion ≈ 61 × log10 ([ion]outside / [ion]inside), with E in millivolts.
The factor 61 (sometimes taught as 58 or 61.5 depending on temperature rounding) comes from RT/F converted to base-10 log at physiologic temperature. You do not need to derive RT/F in the lab. You do need to put real concentrations into the ratio instead of staring at an unexplained formula.
Use the table: [K+]outside = 4 mmol/L, [K+]inside = 140 mmol/L.
- Form the concentration ratio: 4 / 140 = 0.0286.
- Take the base-10 logarithm: log10(0.0286) ≈ −1.54 (because 10 to the −1.54 is about 0.029).
- Multiply by 61: 61 × (−1.54) ≈ −94 mV.
So EK is about −90 to −95 mV with these typical teaching values. If the membrane were a pure K+ electrode, RMP would sit there.
Now Na+ with 145 mmol/L outside and 15 mmol/L inside: ratio 145/15 ≈ 9.67; log10(9.67) ≈ 0.985; 61 × 0.985 ≈ +60 mV. ENa is about +55 to +70 mV. Rest is not +60 mV, so rest cannot be a Na+-selective membrane.
If someone hands you the Nernst equation without a worked ion, you cannot tell whether rest should be near −90 mV or +60 mV. Always plug K+ in as the first example: high inside, low outside, negative EK.
A second micro-example shows why extracellular K+ is potent. If [K+]outside rose from 4 to 8 mmol/L with [K+]inside still 140, the ratio would be 8/140 = 0.057; log10(0.057) ≈ −1.24; 61 × (−1.24) ≈ −76 mV. EK itself depolarized by nearly 20 mV. That is a Nernst shift, not a mysterious toxin effect. Falling extracellular K+ does the opposite: EK becomes more negative and rest can hyperpolarize.
Driving force on an ion is Vm minus that ion's Nernst potential. At a rest of −80 mV, K+ driving force is small (Vm is near EK) so the large PK produces only a modest outward trickle. Na+ driving force is huge (Vm is far from ENa) but PNa is tiny, so inward Na+ leak stays small. The two leaks nearly balance, which is why rest can be stable for hours.
Goldman–Hodgkin–Katz: permeability chooses which Nernst potential wins
Real axons are permeable to more than one ion. The Goldman–Hodgkin–Katz (GHK) relation is a permeability-weighted blend of the Nernst potentials. You do not need an unexplained equation dump; you need the weighting idea.
At rest, potassium permeability (PK) far exceeds sodium permeability (PNa). Leak K+ channels are open; voltage-gated Na+ channels are mostly closed. GHK therefore parks RMP close to EK, typically −70 to −90 mV, a little positive to EK because of a small Na+ leak (and chloride in some cells). Raise PNa, and voltage moves toward ENa — that is depolarization during the AP upstroke. Raise PK still further, and voltage moves toward EK — that is hyperpolarization.
This is also why extracellular potassium is so potent. Increasing [K+]outside shrinks the K+ ratio, makes EK less negative, and depolarizes rest. Decreasing [K+]outside does the opposite. You do not need a chemistry panel to use the concept: the ion the membrane is most permeable to, at the concentrations present, sets the voltage.
The Na+/K+ ATPase: 3 sodium out, 2 potassium in
Gradients would run down if Na+ kept leaking in and K+ kept leaking out. The sodium–potassium pump (Na+/K+ ATPase) burns adenosine triphosphate (ATP) to export 3 Na+ and import 2 K+ each cycle. Two jobs follow.
First, it maintains the millimolar gradients that Nernst potentials assume. After repetitive firing, extra Na+ has entered and extra K+ has left local spaces; the pump restores those inventories so later APs still have driving force.
Second, the 3-out/2-in stoichiometry is electrogenic: one net positive charge leaves per cycle, adding a few millivolts of interior negativity. That contribution is real but small compared with the K+ diffusion potential.
Exam trap: treating the pump as the only reason the interior is negative. If you pharmacologically stop the pump, RMP does not instantly collapse to 0 mV. Existing gradients and open K+ channels still set voltage for a while; then gradients slowly dissipate and the axon becomes inexcitable as Na+ channels inactivate in the depolarized state. Moment-to-moment rest is a permeability story (K+ leak dominating). The pump is the slow restoration system. Mixing those time scales is a favorite wrong-answer pattern.
A related trap is reversing pump direction in memory: it is 3 Na+ out and 2 K+ in, not the reverse. The reverse would destroy the very gradients NCS physiology depends on. Ischemia or metabolic failure that starves ATP eventually lets gradients run down; that is a minutes-to-hours problem, not the mechanism of a 1 ms spike.
Charge layers, not bulk electroneutrality myths
Only a thin veneer of extra positives sits just outside the membrane, and a thin veneer of extra negatives (impermeant organic anions left behind when K+ leaked out) sits just inside. Bulk axoplasm and bulk extracellular fluid remain essentially electroneutral. Surface electrodes sit in that extracellular space. They never read −70 mV RMP. They read how extracellular current changes when many axons depolarize from rest.
That is why a technically perfect NCS baseline can look electrically quiet even though every axon under the electrodes is holding tens of millivolts of rest. Quiet baseline means no synchronized extracellular current yet, not that membranes are uncharged.
From rest to the recorded SNAP and CMAP
Picture a sensory nerve under a cathode. Axons are at −70 to −90 mV. Stimulus current depolarizes a patch of membrane (makes it less negative). If enough axons reach threshold, voltage-gated Na+ current explodes inward, intracellular voltage races toward ENa, and current loops through the extracellular volume conductor. Recording electrodes see a summed biphasic or triphasic field: the SNAP. Motor axons doing the same thing ultimately depolarize muscle fibers; the summed muscle field is the CMAP.
Amplitude of those compound potentials is graded with recruitment (how many axons fire) even though each axon that fires does so all-or-none. That distinction is the next section. The point here is simpler: no organized rest, no organized departure from rest, no SNAP or CMAP. Demyelination, axonal loss, and neuromuscular transmission failure all act on this same resting machine; they do not replace it.
OpenExamPrep emphasis for the laboratory: know which ion is where, know that K+ permeability dominates rest, know the pump stoichiometry, and be able to work a K+ Nernst example to about −90 mV. Those four items explain why your baseline is electrically quiet until a suprathreshold stimulus recruits axons from rest.
At a typical axonal resting potential of about −70 to −90 mV, what mainly sets the voltage from millisecond to millisecond?
Using standard neurophysiology teaching values, which statement about Na+ and K+ is correct?
Using typical teaching concentrations of 4 mmol/L K+ outside and 140 mmol/L K+ inside, which value is closest to the potassium Nernst potential?