What Really Powers Your Nerve Signals? The Secret Life of Action Potentials Under Heat Stress Has Always Been in Plain Sight

Action potentials are rapid electrical signals used by excitable cells—like neurons, muscle fibers, and some endocrine cells—to communicate or trigger processes such as contraction or secretion. In the context of cellular respiration and thermal stress, action potentials become tightly linked to the energy status and ion homeostasis of the cell, particularly due to the role of proton gradients, ATP generation, and membrane dynamics.

1. Bioenergetic Foundation of Action Potentials

Resting membrane potential, the baseline electrical state of a cell (~–70 mV in neurons), is largely established by:

• Na⁺/K⁺-ATPase: Uses ATP from cellular respiration to actively pump 3 Na⁺ out and 2 K⁺ in.

• Selective permeability: At rest, the membrane is more permeable to K⁺, so K⁺ leaks out, making the inside negative.

Action potentials occur when this resting potential is transiently reversed:

• Voltage-gated Na⁺ channels open, Na⁺ floods in → depolarisation.

• Voltage-gated K⁺ channels open, K⁺ flows out → repolarisation.

This cycle requires that ATP levels remain adequate, and ion gradients remain steep, both of which depend on intact mitochondrial respiration and membrane integrity.

2. Link to Cellular Respiration

Cellular respiration—particularly oxidative phosphorylation—supplies ATP, which is critical for:

• Maintaining ion gradients (Na⁺/K⁺-ATPase).

• Powering Ca²⁺ pumps that restore intracellular calcium post-excitation.

• Supporting the metabolic demand of repolarisation and neurotransmitter release.

If ATP becomes scarce, such as during:

• Mitochondrial dysfunction,

• High thermal stress with elevated proton leak and uncoupling,

• Phosphate depletion from hyperactive ATP turnover,

then action potential propagation is impaired:

• Membrane potential may depolarise chronically.

• Ion channel kinetics slow.

• Neurons or muscle fibers become less excitable or even non-functional (e.g., in heat stroke or metabolic collapse).

3. Thermal Stress, Proton Dynamics, and Action Potentials

Under mild hyperthermia, as outlined in the article:

• Membrane fluidity increases, altering ion channel gating:

• Voltage-gated Na⁺ and K⁺ channels open more easily and stay open longer.

• TRP channels may activate, further affecting membrane potential.

• Passive H⁺ leak rises, subtly depolarising membranes and reducing the proton motive force.

• ATP synthase becomes less efficient due to proton slippage or uncoupling, decreasing ATP yield.

• Na⁺/K⁺-ATPase may struggle, compromising ion gradient maintenance.

Net effect: Action potential fidelity declines due to both energy limitation and biophysical instability of ion channels.

This can manifest as:

• Muscle weakness

• Neural fatigue

• Cardiac arrhythmias

• Heat-induced seizures

Example: Neurons in Heat Stress

A febrile state (e.g., 40°C body temperature) might:

1. Increase Na⁺ channel open probability.

2. Lead to spontaneous depolarisations.

3. Overload mitochondria due to heightened ATP demand.

4. Eventually suppress action potential propagation if ATP is depleted or membrane potential collapses.