Membrane Transport in Nerves and Muscles: From Ion Flow to Electrical Signals

Excitability as a Transport Problem

Nerves and muscles are “excitable” because their membranes contain ion channels that can rapidly change permeability. When permeability changes, ions move down their electrochemical gradients, and that ion flow changes the membrane potential. In this chapter, treat each electrical event as a sequence of transport events: which channels open, which ions move, and how the resulting current shifts voltage.

Two ideas guide everything here:

• Gradients store potential energy (concentration differences plus electrical forces).
• Channels control access to those gradients by changing membrane conductance (how easily ions cross).

Key Players in Nerve and Muscle Signaling

Voltage-gated Na⁺ channels: fast inward current

When these channels open, Na⁺ tends to move into the cell (typically down both its concentration and electrical gradients). This inward positive charge makes the inside less negative (depolarizes).

Voltage-gated K⁺ channels: delayed outward current

When these channels open, K⁺ tends to move out of the cell. This outward positive charge makes the inside more negative (repolarizes) and can overshoot (afterhyperpolarization) if K⁺ conductance stays high.

Voltage-gated Ca²⁺ channels: coupling electricity to action

Ca²⁺ entry is a transport event with a large driving force in many cells. The key point is not the downstream biochemistry, but the transport logic: opening Ca²⁺ channels allows Ca²⁺ to enter, and that influx acts as a trigger signal that links membrane depolarization to secretion (neurons) or contraction (muscle).

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Event 1: Resting State (Stable Gradients, Selective Permeability)

At rest, the membrane potential is stable because net ionic currents are small and balanced. This does not mean ions stop moving; it means that for each ion, the driving force and the available conductance produce currents that sum to near zero.

Transport view of resting stability

• Conductance pattern: resting membranes are typically more permeable to K⁺ than to Na⁺, so K⁺ “dominates” the resting potential.
• Leak currents: small Na⁺ leak inward and K⁺ leak outward can coexist; the resting voltage is where the net current is minimal.
• Pumps maintain gradients: ATP-dependent transporters maintain the long-term Na⁺ and K⁺ gradients that make rapid electrical signaling possible. During a single action potential, the gradients change only slightly; over time, pumps restore them.

Practical checkpoint

If you change extracellular ion concentrations, you change gradients, which changes driving forces, which shifts resting voltage and excitability. This becomes clinically important for K⁺ (see below).

Event 2: Depolarization (Positive Feedback via Na⁺ Channel Opening)

Depolarization begins when a stimulus increases inward current (often by opening ligand-gated channels at synapses or mechanically sensitive channels in sensory endings). If depolarization reaches a threshold, voltage-gated Na⁺ channels open in large numbers.

Step-by-step: how Na⁺ influx creates the upstroke

1. Initial depolarization: a small inward current makes the membrane potential less negative.
2. Voltage-gated Na⁺ channels activate: depolarization increases Na⁺ conductance.
3. Na⁺ moves inward: because the electrochemical gradient favors entry, Na⁺ influx accelerates.
4. Positive feedback: more depolarization opens more Na⁺ channels, producing the rapid rising phase of the action potential.

Why the signal propagates

Na⁺ entry at one patch of membrane creates local current flow along the membrane that depolarizes adjacent regions. If those neighboring regions reach threshold, their Na⁺ channels open too. This is a transport-based chain reaction: sequential increases in Na⁺ conductance along the axon or muscle membrane.

Event 3: Repolarization (K⁺ Efflux Restores Negativity)

Repolarization is the return toward the resting voltage. It occurs because the inward Na⁺ current diminishes while outward K⁺ current increases.

Step-by-step: how K⁺ efflux ends the spike

1. Na⁺ current falls: voltage-gated Na⁺ channels stop contributing strong inward current (they inactivate after opening).
2. Voltage-gated K⁺ channels open: they activate more slowly than Na⁺ channels, so their effect peaks later.
3. K⁺ moves outward: outward movement of positive charge drives the membrane potential back negative.
4. Afterhyperpolarization (often): if K⁺ conductance remains elevated briefly, the membrane can become more negative than at rest, making immediate re-firing harder.

Refractory periods as a transport consequence

• Absolute refractory period: many Na⁺ channels are inactivated and cannot reopen, limiting inward current regardless of stimulus.
• Relative refractory period: elevated K⁺ conductance increases outward current; a stronger depolarizing stimulus is needed to overcome it.

Ca²⁺ Entry: Converting Electrical Events into Output

Neurotransmitter release: depolarization opens Ca²⁺ channels

At presynaptic terminals, an arriving action potential depolarizes the membrane and opens voltage-gated Ca²⁺ channels. Ca²⁺ flows into the terminal down a strong electrochemical gradient. That Ca²⁺ influx is the key transport trigger that initiates vesicle fusion and neurotransmitter release.

Muscle contraction: Ca²⁺ as the coupling ion

In muscle, depolarization ultimately increases cytosolic Ca²⁺ to activate contraction. The transport emphasis is: electrical signals change membrane channel states, which changes Ca²⁺ movement. In many muscle types, Ca²⁺ entry through membrane channels and/or Ca²⁺ release from internal stores increases cytosolic Ca²⁺, enabling force generation.

Practical Connection 1: Why Extracellular K⁺ Disturbances Cause Weakness or Arrhythmias

Because resting potential depends strongly on the K⁺ gradient, changing extracellular K⁺ changes the driving force for K⁺ and shifts resting membrane potential. That shift alters how close the membrane sits to threshold and how many Na⁺ channels are available to open.

High extracellular K⁺ (hyperkalemia): depolarizes but can reduce excitability

• Transport logic: raising extracellular K⁺ reduces the outward driving force for K⁺ efflux, so the resting potential becomes less negative (depolarizes).
• Why weakness can occur: sustained depolarization increases the fraction of Na⁺ channels in the inactivated state, reducing the available inward Na⁺ current for action potentials.
• Why arrhythmias can occur: altered resting potential and repolarization dynamics change conduction velocity and refractoriness in cardiac tissue, promoting abnormal rhythms.

Low extracellular K⁺ (hypokalemia): hyperpolarizes and disrupts repolarization

• Transport logic: lowering extracellular K⁺ increases the outward driving force for K⁺, often making the resting potential more negative (hyperpolarizes).
• Why weakness can occur: being farther from threshold makes it harder to trigger action potentials in skeletal muscle.
• Why arrhythmias can occur: changes in K⁺ conductance and driving force can prolong or destabilize repolarization in cardiac cells, increasing susceptibility to ectopic activity.

Step-by-step clinical reasoning shortcut

1. Ask: did extracellular K⁺ go up or down?
2. Predict: resting potential shifts toward less negative (K⁺ up) or more negative (K⁺ down).
3. Translate to channel availability: sustained depolarization reduces available Na⁺ channels; hyperpolarization increases availability but raises threshold distance.
4. Predict tissue effect: skeletal muscle weakness and/or cardiac conduction/repolarization instability.

Practical Connection 2: How Local Anesthetics Block Nerve Signaling

Local anesthetics prevent pain signals from propagating by interfering with voltage-gated Na⁺ channels. The transport framing is straightforward: if Na⁺ channels cannot conduct, the membrane cannot generate the rapid inward Na⁺ current needed for the action potential upstroke.

Step-by-step: from Na⁺ channel block to loss of sensation

1. Drug reaches nerve membrane: local anesthetic molecules diffuse to the axon.
2. Na⁺ channel conductance decreases: fewer functional channels means lower maximum inward Na⁺ current.
3. Threshold becomes harder to reach: a given stimulus produces less depolarizing current relative to outward/leak currents.
4. Action potential fails or shrinks: without sufficient Na⁺ influx, depolarization cannot regenerate along the axon.
5. Propagation stops: the signal cannot reach the CNS, so pain is not perceived.

Use-dependence as a transport-relevant feature

Many local anesthetics block Na⁺ channels more effectively when channels open frequently. Functionally, rapidly firing pain fibers are preferentially suppressed because repeated opening provides more opportunities for block, reducing cumulative Na⁺ transport during trains of impulses.

Putting the Events Together: A Transport Timeline

Rest:   high K+ conductance dominates → stable negative Vm (small net current) Stimulation: inward current begins → Vm depolarizes Threshold: many voltage-gated Na+ channels open → large Na+ influx (positive feedback) Peak:   Na+ channels inactivate; K+ channels open more → inward current falls, outward rises Fall:   K+ efflux repolarizes Vm After:  K+ conductance may remain high → afterhyperpolarization; Na+ channels recover from inactivation Output: Ca2+ channels open where present → Ca2+ influx triggers release/contraction