A researcher applies ouabain, a Na+/K+-ATPase inhibitor, to a neuron. What are the correct immediate and long-term effects on resting membrane potential?
AImmediate large depolarization, because the pump directly generates the negative resting potential
BNo immediate change, but gradual depolarization over minutes to hours as ion gradients slowly dissipate
CImmediate hyperpolarization, because blocking the pump allows K+ to accumulate inside
DNo change at all, because the pump plays no role in setting resting membrane potential
The resting potential is created by passive K+ flow through leak channels, not by the pump directly. Stopping the pump immediately eliminates its small electrogenic contribution (~few mV) but leaves ion gradients — and therefore K+ leak — essentially intact. Over minutes to hours, however, the gradients dissipate (Na+ leaks in, K+ leaks out) because no pump is restoring them, and the membrane potential gradually depolarizes toward zero. Option A represents the key misconception: the pump is not the direct generator of the resting potential.
Question 2 Multiple Choice
Why is the resting membrane potential approximately −70 mV rather than the K+ equilibrium potential of about −90 mV?
AThe Na+/K+-ATPase pump adds +20 mV directly to the K+ equilibrium potential
BSmall but finite membrane permeability to Na+ allows a slight inward Na+ current that partially offsets K+ efflux, pulling the potential toward Na+'s equilibrium of +60 mV
CK+ leak channels are partially blocked at rest, preventing full K+ equilibration
DThe cell expends ATP to actively clamp the membrane at −70 mV rather than at the K+ equilibrium
The resting potential is a weighted average of the equilibrium potentials for all permeant ions, weighted by their relative permeabilities. At rest, the membrane is highly permeable to K+ (equilibrium ~−90 mV) and slightly permeable to Na+ (equilibrium ~+60 mV). The small Na+ leak pulls the actual potential ~20 mV positive of the K+ equilibrium potential. The Goldman equation formalizes this. The pump's direct electrogenic contribution is only 2–3 mV, not 20 mV.
Question 3 True / False
The Na+/K+-ATPase pump directly creates the resting membrane potential by pumping charge across the membrane, generating the −70 mV gradient.
TTrue
FFalse
Answer: False
This is the most common misconception about resting membrane potential. The pump's primary role is maintaining ion concentration gradients, not directly generating voltage. The resting potential is created by passive K+ flow through leak channels: K+ moves out down its concentration gradient until the developing electrical force (inside becoming negative) exactly balances the chemical force. Blocking the pump with ouabain has little immediate effect on resting potential — gradients persist and K+ continues to flow passively. The pump's direct electrogenic effect (3 Na+ out for 2 K+ in) contributes only ~2–3 mV.
Question 4 True / False
If K+ leak channels were suddenly and completely blocked, the resting membrane potential would collapse toward zero even if the Na+/K+-ATPase pump continued operating normally.
TTrue
FFalse
Answer: True
The resting potential exists because K+ flows passively through open leak channels until electrical and chemical forces balance. The pump maintains the concentration gradient that drives this flow, but if the channels are blocked, no K+ movement occurs regardless of the gradient — and without K+ movement, the voltage difference is not created or maintained. The pump cannot substitute for channel-mediated current. This thought experiment reveals that the channels, not the pump, are the proximate generators of the resting potential.
Question 5 Short Answer
Why is the resting membrane potential closer to the K+ equilibrium potential than to the Na+ equilibrium potential, even though both ions have steep concentration gradients across the membrane?
Think about your answer, then reveal below.
Model answer: At rest, the membrane is highly permeable to K+ due to abundant open K+ leak channels, while Na+ channels are mostly closed. K+ flows out down its concentration gradient, generating most of the membrane's negative interior voltage and pulling the potential toward K+'s equilibrium (~−90 mV). Na+ has a large driving force (toward +60 mV) but little membrane permeability at rest, so its influence is minor. Resting potential (~−70 mV) reflects this imbalance — it is weighted primarily by K+ permeability, with a slight positive shift from the small Na+ leak.
The Goldman equation formalizes this: membrane potential is a permeability-weighted average of equilibrium potentials. The dominant K+ permeability at rest makes the potential closely track E_K. During an action potential, Na+ channels open massively, temporarily making Na+ the dominant ion and driving the potential toward +60 mV before K+ repolarizes the cell.