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

Explanation

## 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 - **K+ permeability is ~25 times higher than Na+ permeability at rest**, making K+ the dominant determinant of RMP via the GHK equation. - **RMP ≈ −70 mV** in neurons is primarily due to passive K+ efflux down its concentration gradient (high inside, low outside). - **Na+/K+-ATPase pump** maintains ion gradients (3 Na+ out, 2 K+ in) but contributes only ~5–10 mV directly to RMP via its electrogenic effect. - **Hyperkalemia depolarizes** (raises RMP toward 0), increasing cardiac excitability and causing life-threatening arrhythmias—a critical Indian ICU emergency. - **Cl− is passively distributed** and does not set RMP; its Nernst potential (~−70 mV) matches RMP by coincidence, not causation. ## 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)_