Which ion is most responsible for the resting membrane potential (RMP)?

Correct Answer: D. Potassium (K+)

The resting membrane potential (RMP) of approximately −70 mV in neurons is primarily determined by potassium (K+), not because it is the only ion involved, but because the neuronal membrane is most permeable to K+ at rest. The Goldman-Hodgkin-Katz (GHK) equation mathematically demonstrates that RMP is weighted most heavily by the ion with the highest membrane permeability. At rest, K+ permeability is _{25 times greater than Na+ permeability, making K+ the dominant contributor. K+ concentration is high intracellularly (}140 mEq/L) and low extracellularly (_{5 mEq/L), creating a large concentration gradient. The Na+/K+-ATPase pump actively maintains these gradients by pumping 3 Na+ out and 2 K+ in, consuming ATP. While the pump itself generates a small hyperpolarizing current (electrogenic effect,} −5 to −10 mV), the bulk of RMP arises from passive K+ efflux down its concentration gradient through leak channels. Cl− and Ca2+ have minimal roles: Cl− is passively distributed and follows the potential set by K+ and Na+, while Ca2+ permeability is negligible at rest. In Indian clinical practice, understanding K+ dominance is critical for recognizing hyperkalemia (which depolarizes the membrane, causing cardiac arrhythmias) and hypokalemia (which hyperpolarizes, causing muscle weakness and arrhythmias)—both common electrolyte emergencies in Indian hospital settings.

Why the other options are wrong

A. Chloride (Cl-) — Chloride is a passively distributed anion that does not establish RMP; instead, it distributes itself according to the potential set by K+ and Na+. Although Cl− permeability is significant in some tissues (e.g., skeletal muscle), it is secondary to K+ in determining RMP. The Nernst potential for Cl− is approximately −70 mV, which matches RMP by coincidence, not causation—a classic NBE trap. Students confuse matching equilibrium potentials with causal responsibility. B. Sodium (Na+) — Sodium has a Nernst potential of approximately +60 mV, which would depolarize the cell if Na+ were the dominant permeant ion. At rest, Na+ permeability is ~25 times lower than K+ permeability, so Na+ influx is minimal. The Na+/K+-ATPase pump does extrude Na+, but this is an active, energy-dependent process that maintains the gradient—not the passive mechanism driving RMP. Confusing the pump's role with RMP determination is a common student error. C. Calcium (Ca2+) — Calcium permeability is negligible at rest in most neurons; Ca2+ channels are closed and contribute minimally to RMP. Ca2+ becomes important during action potentials (in some tissues like cardiac pacemaker cells) and in synaptic transmission, but not in establishing baseline RMP. Students may incorrectly recall Ca2+ as important in excitability and mistakenly select it, confusing its role in changing potential with establishing resting potential.

High-Yield Facts

Mnemonics

*PERMEABILITY RULES RMP At rest, K+ permeability >> Na+ permeability. Whichever ion is most permeable dominates RMP. K+ is 25× more permeable, so K+ wins. Use this when deciding between K+ and Na+. GHK = Weighted Average* Goldman-Hodgkin-Katz equation: RMP is a weighted average of all ion Nernst potentials, weighted by their permeabilities. K+ has the highest weight → K+ dominates. Recall this when asked 'which ion determines RMP.'

NBE Trap

NBE pairs Cl− with RMP by noting that Cl− Nernst potential (~−70 mV) matches the observed RMP value, luring students into thinking Cl− is responsible. The trap: matching a number ≠ causation. K+ is causal; Cl− is coincidental. Additionally, students confuse the Na+/K+-ATPase pump's active role in maintaining gradients with its passive role in setting RMP—the pump is necessary but not the primary driver of the resting potential itself.

Clinical Pearl

In Indian emergency departments, acute hyperkalemia (K+ >6.5 mEq/L, common in acute kidney injury and rhabdomyolysis) causes membrane depolarization, manifesting as peaked T waves, widened QRS, and potentially fatal ventricular fibrillation. Conversely, hypokalemia (K+ <3.5 mEq/L, seen in diarrhea, diuretic use, and malnutrition) hyperpolarizes the membrane, causing muscle weakness and U waves on ECG. Both underscore K+'s primacy in determining excitability and RMP.

_Reference: Guyton & Hall Textbook of Medical Physiology, Ch. 5 (Membrane Potentials and Action Potentials); Harrison's Principles of Internal Medicine, Ch. 366 (Electrolyte Disorders)_