BIO310 Lec 5

What type of graded potential is required to elicit an action potential (AP)?

A strong depolarized graded potential.

Can a hyperpolarized graded potential generate an action potential?

No, a hyperpolarized GP cannot trigger an AP.

How can a depolarized graded potential trigger an action potential?

If it summates with other GPs and reaches threshold at the axon hillock.

Where are graded potentials generated?

In dendrites and the cell body.

Why does GP strength decrease with distance?

Due to local resistance and leakage through K⁺ channels.

What happens when GPs reach the axon hillock?

If the GP is strong enough to open enough NaV channels, threshold is reached and an AP forms.

What causes graded potentials to be generated?

Ligand-gated ion channels.

What opens voltage-gated sodium (NaV) channels?

Depolarization — positive charge near the channel.

What occurs if threshold is not reached?

The depolarization dies out due to repolarization.

What happens if threshold is reached?

All NaV channels open, Na⁺ influx occurs, and the rising phase of the AP begins.

Which ion channels are necessary for AP generation and completion?

Voltage-gated Na⁺ (NaV) and K⁺ (KV) channels.

What happens during repolarization?

KV channels open, allowing K⁺ efflux, which reduces positive charge.

What makes KV channels slower than NaV channels?

They open at the peak of the AP, have slower voltage sensors, and close slowly.

What unique feature do NaV channels have?

An inactivation loop between domains 3 & 4 that blocks Na⁺ entry even when the channel is open.

Why can the membrane potential never reach Ena (+60 mV)?

Because NaV channel inactivation prevents further Na⁺ influx.

Which two types of voltage-gated channels are involved in APs?

NaV (sodium) and KV (potassium) channels.

Where are proteins for ion channels synthesized?

In the rough ER.

How do proteins fold into functional channels?

They form primary, secondary, and tertiary structures, then are directed by the Golgi apparatus into vesicles for membrane expression.

How many domains does a NaV channel have?

Four domains, each with six transmembrane helices.

Which helix acts as the voltage sensor?

Helix 4 (contains positive charges).

What are P-loops in NaV channels responsible for?

Ion selectivity (Na⁺ specificity).

What is the typical resting membrane potential (RMP)?

Around –70 mV.

At what membrane potential do NaV channels fully open (threshold)?

About –55 mV.

What is the peak of the AP?

+30 mV (maximal Na⁺ permeability).

What happens at +30 mV?

KV channels open, leading to repolarization and hyperpolarization.

What restores ion gradients after an AP?

The Na⁺/K⁺ ATPase pump.

What type of feedback is involved in depolarization?

Positive feedback (Hodgkin cycle).

What type of feedback is involved in repolarization?

Negative feedback (K⁺ efflux reducing Vm).

What is the absolute refractory period?

The time after the AP peak through repolarization when NaV channels are inactivated and no new AP can be generated.

What is the relative refractory period?

During hyperpolarization, when a stronger-than-threshold stimulus can generate a new AP.

How does stimulus strength affect APs?

Stronger stimuli increase AP frequency, not amplitude.

Why do APs propagate in only one direction?

Because of NaV inactivation and refractory periods preventing backward conduction.

What affects the velocity of AP propagation?

Axon diameter and myelination.

What is saltatory conduction?

APs jumping between nodes of Ranvier in myelinated axons.

What is the function of nodes of Ranvier?

They contain NaV, KV channels, and Na/K pumps, allowing AP regeneration.

What is convergence?

Multiple neurons influencing one postsynaptic neuron.

What is divergence?

One neuron influencing multiple postsynaptic neurons.

What are gap junctions?

Electrical synapses allowing direct ion flow between adjacent neurons.

What characterizes chemical synapses?

A synaptic cleft, neurotransmitter release via regulated exocytosis, and postsynaptic receptors.

What are the steps of neurotransmitter release?

1) NT synthesis, 2) AP invades presynaptic terminal, 3) depolarization opens CaV channels, 4) Ca²⁺ influx, 5) vesicle fusion with membrane, 6) NT release, 7) receptor binding, 8) postsynaptic current (EPSP/IPSP), 9) NT removal, 10) vesicle recycling.

What proteins mediate vesicle docking and fusion?

Synaptobrevin (vesicle SNARE), synaptotagmin (Ca²⁺ sensor), syntaxin (membrane SNARE), Munc18, and SNAP-25.

What prevents vesicle fusion until Ca²⁺ binds?

Complexin, which is displaced when Ca²⁺ binds synaptotagmin.

What are the two methods of vesicle fusion?

Kiss-and-run (partial fusion) and classical full fusion.

What is temporal summation?

Multiple GPs arriving close in time, increasing the chance of AP firing.

What is spatial summation?

Multiple neurons simultaneously influencing a postsynaptic neuron.

What is the typical excitatory neurotransmitter in the CNS?

Glutamate.

What are the typical inhibitory neurotransmitters in the CNS?

GABA and glycine.

What is contained in one vesicle at the neuromuscular junction?

~5000 molecules of ACh (one quantum).

What are neuromodulators?

Chemical messengers that act mainly via GPCRs, modulating neuronal activity (e.g., dopamine, serotonin, ACh).

Where are small-molecule NTs synthesized?

In the axon terminal.

Where are large neuropeptide NTs synthesized?

In the cell body, transported via microtubules.

How is acetylcholine synthesized?

From choline + acetyl-CoA, catalyzed by choline acetyltransferase (ChAT).

How is acetylcholine degraded?

By acetylcholinesterase into choline (recycled) and acetate (diffuses away).

What are biogenic amines?

Small charged molecules derived from amino acids, e.g., dopamine, norepinephrine, epinephrine, serotonin, histamine.

Which neurotransmitters are catecholamines?

Dopamine, norepinephrine, epinephrine (all derived from tyrosine).

What is serotonin derived from?

Tryptophan.

Where is most serotonin found?

~90% in the gastrointestinal tract, some in platelets and immune cells, only 1–2% in the brain.

How many serotonin receptors exist?

16 different receptor types across the brain, spinal cord, and body.

How does serotonin influence appetite?

Increased serotonin suppresses hunger; low serotonin increases food intake.

How is serotonin signaling terminated?

By reuptake into the presynaptic terminal and/or degradation by monoamine oxidase (MAO).

How is depression related to serotonin?

Low serotonin activity is linked to depression.

How can serotonin availability be increased to treat depression?

Using SSRIs (block reuptake) or MAOIs (block degradation