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Resting membrane potential depends on
Ion concentration gradients (chemical force), electrical forces, pumps, and membrane permeability (mainly K⁺ through leak channels)
Graded potential
A small change (under ~20 mV) in membrane potential away from rest; can be excitatory (depolarising) or inhibitory (hyperpolarising)
Size of a graded potential depends on
The intensity (strength) of the stimulus
Key difference: graded vs action potential spreading
Graded potentials SHRINK as they spread; action potentials do NOT
Action potential (AP)
A rapid, large but brief depolarisation that is propagated (spreads along the membrane)
Which cells have action potentials?
Neurons and all muscle cells (skeletal, smooth, cardiac)
All-or-none principle
Once threshold is reached, an AP fires fully; if threshold isn't reached, no AP fires at all
Threshold
The membrane voltage that must be reached to trigger an action potential
AP Phase 1: depolarisation
At threshold, voltage-gated Na⁺ channels open; Na⁺ rushes in; Vm rises toward E Na (~+60 mV)
Why is depolarisation positive feedback?
Depolarisation opens Na⁺ channels → more depolarisation → opens even more Na⁺ channels
Why doesn't the AP peak reach E Na?
Voltage-gated Na⁺ channels inactivate before Vm gets there (and K⁺ channels are opening)
AP Phase 2: repolarisation
Voltage-gated K⁺ channels open; K⁺ rushes out (pushed by its gradient and the now-positive inside); with Na⁺ channels inactivated, Vm falls
AP Phase 3: hyperpolarisation (undershoot)
K⁺ keeps leaving, so Vm becomes more negative than rest, moving toward E K; voltage-gated K⁺ channels close before reaching E K
What restores resting potential after an AP?
Leak channels
Role of the Na⁺/K⁺ pump during APs
Maintains the concentration gradients over many action potentials (not needed for each single AP)
Two gates of the voltage-gated Na⁺ channel
Activation gate and inactivation gate
Na⁺ activation gate
Closed at rest; opens FAST when the membrane reaches threshold
Na⁺ inactivation gate
Closes after a brief delay (time-dependent) at threshold; stays closed until the membrane returns to resting potential ('ball and chain')
Three states of the voltage-gated Na⁺ channel
Rest: closed but able to open → Threshold to peak: open → Peak back to rest: inactivated (closed, can't open)
Voltage-gated K⁺ channels
Closed at rest; opened by depolarisation but open more SLOWLY than Na⁺ channels; close slowly → cause the undershoot
Why does Na⁺ win when both Na⁺ and K⁺ channels are briefly open?
Na⁺ permeability is much greater at that moment
Absolute refractory period
NO action potential can be generated, however strong the stimulus; occurs during depolarisation and repolarisation
Cause of the absolute refractory period
Na⁺ inactivation gates are closed, so no Na⁺ can enter
Relative refractory period
An AP CAN fire, but only with a STRONGER stimulus; occurs during hyperpolarisation
Why do refractory periods matter?
They make APs travel one way and limit how fast a neuron can fire
Depolarisation block
Sustained depolarisation keeps Na⁺ inactivation gates closed → APs weaken then fail
Mild vs severe hyperkalaemia on excitability
Mild: closer to threshold → INCREASED excitability. Severe/sustained: Na⁺ channels inactivated → DECREASED excitability (depolarisation block)
Why can severe hyperkalaemia be fatal?
Depolarisation block in the heart → slowed conduction, bradycardia, arrhythmias, cardiac arrest
How do local anaesthetics work?
They block voltage-gated Na⁺ channels → no action potential → no pain signal
Similarities of APs across excitable cells
Very rapid depolarisation; all-or-none; roughly the same amplitude; amplitude does not depend on stimulus size
How is stimulus intensity coded?
By the FREQUENCY of action potentials, not their size (amplitude)
Differences of APs between cell types
Speed and complexity (shape) vary, and so does what they trigger
What does an AP trigger in a neuron / muscle / endocrine cell?
Neuron: chemical transmission. Muscle: contraction. Endocrine cell: secretion
Cardiac AP plateau
A long flat phase caused by Ca²⁺ influx balanced by K⁺ efflux
Neuron
A nerve cell that receives, integrates and transmits electrical signals
EPSP
Excitatory postsynaptic potential: a graded potential that DEPOLARISES the membrane
IPSP
Inhibitory postsynaptic potential: a graded potential that HYPERPOLARISES the membrane
Where are EPSPs and IPSPs summed?
At the AXON HILLOCK (trigger zone)
Why does the AP start at the axon hillock?
It has a high density of voltage-gated Na⁺ channels
Summation
Adding together graded potentials so that weak inputs can combine to reach threshold
Temporal summation
Rapid, repeated signals from the SAME input add together over TIME
Spatial summation
Signals from DIFFERENT inputs arriving at the same time add together
What decides whether a neuron fires?
The sum of all EPSPs and IPSPs at the axon hillock reaching threshold
How does an AP propagate along an axon?
Depolarisation opens Na⁺ channels in the next patch of membrane ahead; behind, K⁺ leaves and repolarises
Why does an AP travel in only one direction?
Na⁺ channels just behind the AP are inactivated (refractory)
Axolemma / axoplasm
Axolemma = axon's plasma membrane. Axoplasm = cytoplasm inside the axon
Myelin sheath
Tightly wrapped lipid bilayers plus proteins that insulate and support the axon
Conduction in unmyelinated axons
The AP travels continuously along the membrane (slower)
Nodes of Ranvier
Unmyelinated gaps between myelin segments, where voltage-gated Na⁺ channels cluster to regenerate the AP
Saltatory conduction
The AP 'jumps' from node to node in myelinated axons; much faster
How does myelin speed conduction?
Increases membrane resistance and decreases capacitance, so the depolarising wave decays less
Factors at the nodes that affect speed
Distance between nodes and the number of voltage-gated Na⁺ channels at each node
Range of conduction velocity
About 0.2 to 120 m/s
Two main factors that determine conduction velocity
Axon diameter and myelination
How does a larger axon diameter increase speed?
It decreases internal resistance to current flow along the axon
Fastest type of axon
Large-diameter AND myelinated