Correct Answer: B. Becomes more positive
Resting membrane potential (RMP) is determined by the Nernst equation and the Goldman-Hodgkin-Katz equation, which show that RMP depends on the ratio of intracellular to extracellular ion concentrations, particularly K⁺. Normally, extracellular K⁺ is 5 mEq/L and intracellular K⁺ is 140 mEq/L, maintaining a steep concentration gradient that keeps RMP at approximately −90 mV. In severe muscle injury (rhabdomyolysis from RTA), massive cell lysis releases intracellular K⁺ into the extracellular space, raising serum K⁺ to 5.5 mEq/L. This decreases the K⁺ concentration gradient (ratio becomes less steep). According to the Nernst equation, when the concentration gradient decreases, the equilibrium potential for K⁺ becomes less negative (moves toward 0 mV). Since K⁺ is the dominant ion determining RMP at rest, the RMP becomes less negative or more positive (e.g., from −90 mV toward −80 mV). This hyperkalemia-induced depolarization is a critical clinical problem in trauma and rhabdomyolysis, increasing cardiac arrhythmia risk. The membrane potential moves closer to threshold, increasing excitability initially but paradoxically causing paralysis as sustained depolarization inactivates Na⁺ channels.
Why the other options are wrong
A. Becomes more negative — This is wrong because hyperkalemia decreases the K⁺ concentration gradient, not increases it. A more negative RMP would require a steeper K⁺ gradient (higher extracellular-to-intracellular ratio), which is the opposite of what occurs in rhabdomyolysis. This option reflects confusion about the direction of ion leak in muscle injury. C. First becomes more positive then negative — This is wrong because it misapplies the concept of biphasic response seen in some conditions. While hyperkalemia does cause initial depolarization (more positive), there is no subsequent repolarization to more negative values in acute hyperkalemia. The membrane potential stabilizes at a new, less negative level. This option confuses acute hyperkalemia with conditions like hypoxia that cause biphasic changes. D. No change — This is wrong because it ignores the fundamental principle that RMP is K⁺-dependent. Serum K⁺ elevation directly alters the concentration gradient and thus the equilibrium potential. Any change in extracellular K⁺ concentration must change RMP according to the Nernst equation. This trap catches students who memorize RMP as a fixed value rather than understanding its dynamic basis.
High-Yield Facts
- Nernst equation: RMP becomes less negative when extracellular K⁺ increases because the concentration gradient decreases.
- Hyperkalemia from rhabdomyolysis: Serum K⁺ >5.5 mEq/L causes depolarization and increases risk of cardiac arrhythmias (peaked T waves, prolonged PR interval, widened QRS).
- Normal K⁺ gradient: Extracellular 5 mEq/L, intracellular 140 mEq/L; ratio of ~1:28 maintains RMP at −90 mV.
- Depolarization paradox: Initial hyperkalemia increases excitability (closer to threshold), but sustained depolarization inactivates Na⁺ channels, causing flaccid paralysis.
- RTA + crush injury: Massive muscle necrosis releases K⁺, phosphate, myoglobin; acute kidney injury worsens hyperkalemia by reducing renal K⁺ excretion.
Mnemonics
K⁺ OUT = RMP UP (less negative) When extracellular K⁺ goes UP (out of cells), the concentration gradient goes DOWN, so RMP goes UP (becomes less negative/more positive). Use this in any hyperkalemia scenario. NERNST = Ratio Rule RMP depends on In/Out ratio of K⁺. High extracellular K⁺ shrinks this ratio → RMP moves toward 0 mV (depolarization). Low extracellular K⁺ expands ratio → RMP becomes more negative (hyperpolarization).
NBE Trap
NBE pairs rhabdomyolysis with hyperkalemia to test whether students understand the direction of RMP change via the Nernst equation. The trap is offering "becomes more negative" (option A), which is the intuitive but wrong answer for students who confuse "more K⁺ outside" with "stronger gradient" rather than "weaker gradient."
Clinical Pearl
In Indian trauma centres, hyperkalemia from crush injuries (RTA, building collapse) is a medical emergency. ECG changes (peaked T waves, prolonged PR) appear at K⁺ >6.5 mEq/L; cardiac arrest risk rises sharply. Acute management includes calcium gluconate (membrane stabilization), insulin-glucose, and sodium bicarbonate—all aimed at shifting K⁺ back intracellularly to restore the gradient and RMP.
_Reference: Guyton & Hall Textbook of Medical Physiology, Ch. 5 (Membrane Potentials and Action Potentials); KD Tripathi Essentials of Medical Physiology, Ch. 2 (Nerve and Muscle)_