1 Graded + Action Potentials

A graded potential is a local change in membrane potential whose magnitude varies with stimulus strength and that decreases with distance (decremental).

Graded potentials are often initiated by ligand‑gated (or other stimulus‑gated) channels at synapses or receptors.

They can be depolarizing or hyperpolarizing, and their amplitude is graded (varies with stimulus size); they are also decremental with distance.

Short distances — graded potentials transmit information locally along the membrane and are not used for long‑range signaling.

An action potential is a large, rapid, all‑or‑none change in membrane potential used for long‑distance signaling in excitable cells.

Cells that can produce APs include neurons, muscle cells, and some endocrine cells — these membranes are described as excitable.

Voltage‑gated ion channels (especially voltage‑gated Na+ and K+ channels) are essential — they open/close in response to membrane voltage changes.

Voltage‑gated Na+ channels open and inactivate very rapidly (~0.5 ms) and possess an inactivation gate that stops Na+ influx during the AP.

Voltage‑gated K+ channels open and close more slowly (≈1–3 ms) compared with Na+ channels and contribute to repolarization and hyperpolarization.

APs can change membrane potential by as much as ~100 mV and are very rapid, typically 1–4 ms in duration.

Excitability is the ability of a cell (e.g., neuron or muscle) to generate action potentials.

At rest the membrane potential is ≈ -70 mV; P_K > P_Na due to leak K+ channels and voltage‑gated channels are closed.

The threshold potential is usually around -55 mV; reaching threshold opens voltage‑gated Na+ channels and triggers the AP.

When threshold is reached, voltage‑gated Na+ channels open, allowing rapid Na+ influx which makes the membrane potential less negative (depolarizes toward 0 mV).

Overshoot is when the membrane potential becomes positive (about +30 mV), reversing membrane polarity during the peak of the AP.

As membrane potential becomes positive, the inactivation gate on Na+ channels closes, inactivating the channel and stopping Na+ influx.

Voltage‑gated K+ channels open (slower), allowing K+ efflux which makes the inside more negative and repolarizes the membrane.

K+ channels are slow to close, so K+ permeability remains elevated briefly, causing the membrane to become more negative than RMP (hyperpolarization).

Afterhyperpolarization is the transient period after an AP when PK remains above resting levels, driving the membrane toward the K+ equilibrium potential.

Eventually K+ channels close and the Na+/K+ pump helps maintain and restore the resting membrane potential.

Positive feedback: opening of voltage‑gated Na+ channels increases PNa, causing more Na+ influx and further depolarization, which opens more Na+ channels.

Negative feedback: opening of K+ channels increases PK, causing K+ efflux that repolarizes the membrane and opposes depolarization.

Subthreshold potentials are local membrane changes that are too weak to open voltage‑dependent Na+ channels and therefore do not trigger an AP.

The all‑or‑none principle means once threshold is reached, the AP's size and shape are fixed; action potentials either occur fully or not at all, regardless of suprathreshold stimulus strength.

Local anesthetics block voltage‑gated Na+ channels, preventing Na+ influx and thereby preventing AP generation — this blocks transmission of pain signals.

Stimulus intensity is encoded by the frequency and pattern of AP firing (frequency coding): more intense stimuli produce higher firing rates.

The absolute refractory period is when no second AP can be generated regardless of stimulus strength because Na+ channels are open or inactivated.

Because voltage‑gated Na+ channels are already open or inactivated, they cannot be re‑opened to initiate a new AP.

The relative refractory period follows the absolute period; some Na+ channels have recovered, but the membrane is hyperpolarized, so a larger‑than‑normal stimulus is required to trigger an AP.

Because the membrane is hyperpolarized (more negative than RMP) and some Na+ channels are still inactivated, so depolarization must be greater to reach threshold.

Refractory periods limit the maximal firing rate and ensure unidirectional propagation of APs (the region just activated is refractory, preventing backward propagation).

The AP depolarizes adjacent membrane to threshold, regenerating the AP sequentially along the axon.

Because the membrane behind the AP is in the refractory period, preventing re‑excitation and forcing propagation forward.

Larger diameter axons conduct APs faster because they offer less internal resistance to current flow.

Myelination speeds conduction by reducing charge leakage and enabling saltatory conduction (APs jump node to node), increasing conduction velocity.

Voltage‑gated Na+ channels are concentrated at the nodes of Ranvier, where APs are regenerated.

Saltatory conduction is the process where APs 'jump' from node to node in myelinated axons, greatly increasing conduction speed.

Examples: (1) Amplitude — graded varies, AP is all‑or‑none; (2) Summation — graded can sum, AP cannot; (3) Conduction — graded is decremental, AP is non‑decremental (regenerates).

Graded potentials are often initiated by ligand‑gated or sensory receptors; action potentials are initiated when graded depolarization reaches voltage‑dependent threshold, opening voltage‑gated channels.

The opening and closing of voltage‑gated Na+ and K+ channels determine the time course of PNa and PK during the AP.

Action potentials can repeat at frequencies of several hundred per second in excitable cells.

Because K+ channels open slowly, they contribute to repolarization and afterhyperpolarization; their slow kinetics shape the trailing phase of the AP.

Blocking APs (e.g., with Na+ channel blockers) prevents graded signals from reaching the brain, so pain perception is lost — used in local anesthesia.