Physio 5) Synaptic transmission

What is a synapse?

A specialized junction through which a neuron sends a signal to another cell.

• Presynaptic cell = sends signal

• Postsynaptic cell = receives signal

• Synaptic cleft = space between them

What are the 2 types of synapses?

• Electrical synapse → direct current flow

• Chemical synapse → neurotransmitter release

What is the main difference between electrical and chemical synapses?

Electrical: current passes directly between cells.
Chemical: neurotransmitter crosses a synaptic cleft.

What is an electrical synapse?

A gap junction that allows electrical current to pass directly from one cell to another through channels called connexons.

What are the major properties of electrical synapses?

• very narrow cleft: ~2 nm

• direct ion/current passage

• connexon channels

• bidirectional

• very small delay: ~0.1 ms

Why are electrical synapses useful?

They allow a fast, synchronized response of many cells.

Examples:

• cardiac muscle

• smooth muscle

• some neurons

What are the major properties of chemical synapses?

• larger cleft: 20–60 nm

• neurotransmitter released from presynaptic vesicles

• postsynaptic receptors

• unidirectional

• synaptic delay ~0.5–1 ms

Why is chemical transmission unidirectional?

Neurotransmitter is released from the presynaptic terminal, while its receptors are located on the postsynaptic membrane.

So information normally travels:

presynaptic → postsynaptic

What is synaptic delay?

Time between:

arrival of the AP at the presynaptic terminal

and

change in postsynaptic membrane potential

Chemical synapses: ~0.5–1 ms.

Compare electrical and chemical synapses.

Electrical

• gap junction

• direct current

• ~2 nm cleft

• bidirectional

• ~0.1 ms delay

• synchronized response

Chemical

• neurotransmitter

• 20–60 nm cleft

• unidirectional

• 0.5–1 ms delay

• uses receptors

What signal conversions occur at a chemical synapse?

Presynaptic terminal:

electrical AP → chemical neurotransmitter

Postsynaptic membrane:

chemical neurotransmitter → electrical membrane response

What ion is critical for triggering neurotransmitter release from the presynaptic terminal?

Ca²⁺

Presynaptic voltage-gated Ca²⁺ channels open during depolarization.

What is the neuromuscular junction (NMJ)?

The chemical synapse between a lower α-motor neuron and a skeletal muscle fiber.

What are the three major structural components of the NMJ?

• Presynaptic terminal containing ACh vesicles

• Synaptic cleft, about 50–60 nm

• Postsynaptic motor end plate containing junctional folds and ACh receptors

What is the motor end plate?

The specialized postsynaptic region of skeletal muscle at the NMJ.

It contains:

• junctional folds

• acetylcholine receptors

What does “cholinergic” mean?

A neuron or axon that releases acetylcholine (ACh).

What is the sequence of presynaptic events at the NMJ?

AP reaches motor-neuron terminal
→ terminal depolarizes
→ voltage-gated Ca²⁺ channels open
→ Ca²⁺ enters
→ vesicles fuse with presynaptic membrane
→ ACh released by exocytosis

Which Ca²⁺ channels are mentioned in the lecture as participating in neurotransmitter release?

Voltage-gated:

• N-type

• P/Q-type

Ca²⁺ channels.

What happens to ACh after it is released?

ACh diffuses across the synaptic cleft and binds ACh receptors on the motor end plate.

What type of ACh receptor is found at the skeletal muscle NMJ?

A nicotinic cholinergic receptor.

It is a ligand-gated ion channel.

What is the ligand for the nicotinic receptor at the NMJ?

Acetylcholine.

What ions pass through the nicotinic ACh receptor?

The receptor conducts:

• Na⁺

• K⁺

At the motor end plate, the important net effect is Na⁺ inward current → depolarization.

What is the subunit composition of the nicotinic receptor shown in the lecture?

Five subunits:

• 2 α

• 1 β

• 1 δ

• 1 γ

What is an end plate potential (EPP)?

A graded depolarization of the motor end plate produced mainly by Na⁺ influx through ACh-gated nicotinic receptors.

Is the end plate potential itself an action potential?

No.

The EPP is a graded potential.

If it depolarizes adjacent muscle membrane to threshold, it triggers a muscle action potential.

How does the EPP trigger a muscle action potential?

ACh binds nicotinic receptor
→ Na⁺ enters
→ EPP depolarizes motor end plate
→ nearby sarcolemma reaches threshold
→ fast voltage-gated Na⁺ channels open
→ muscle AP begins.

What ion movements produce the skeletal muscle action potential?

Depolarization: Na⁺ moves into the muscle cell.

Repolarization: K⁺ moves out.

The lecture gives skeletal muscle RMP around −88 mV.

: How is ACh signaling terminated at the NMJ?

Acetylcholinesterase (AChE) breaks ACh into:

• acetate

• choline

This stops ACh receptor activation.

What happens to choline after ACh is broken down?

Choline is taken back into the presynaptic terminal by a Na⁺-choline cotransporter.

How efficient is acetylcholinesterase according to the lecture?

One AChE molecule can degrade about 5,000 ACh molecules per second.

What are the two major families of cholinergic receptors?

1. Nicotinic

2. Muscarinic

ACh is the endogenous agonist for both.

Nicotinic vs muscarinic receptors?

Nicotinic

• ionotropic

• ligand-gated ion channel

• activated by ACh

• nicotine is an exogenous agonist

• rapid

Muscarinic

• metabotropic

• G-protein-coupled receptor

• M1–M5 types

• activated by ACh

• muscarine is an exogenous agonist

Why are muscarinic responses different from nicotinic responses?

Muscarinic receptors signal through G proteins, which then influence ion channels or other intracellular processes instead of forming the ion channel themselves.

What is an agonist?

A substance that binds a receptor and activates its normal response.

Example:

nicotine → nicotinic receptor activation

What is an antagonist?

A substance that binds a receptor but blocks/inhibits its normal response.

Example:

d-tubocurarine → blocks nicotinic receptor activation

What is the endogenous agonist of nicotinic and muscarinic receptors?

Acetylcholine.

What is curare/d-tubocurarine and what does it do at the NMJ?

It is a nicotinic receptor antagonist.

It binds the postsynaptic receptor
→ channel does not open normally
→ Na⁺ inward current/EPP decreases
→ muscle AP and contraction are impaired.

Does an agonist or antagonist at the NMJ act primarily on the presynaptic or postsynaptic membrane in the examples shown?

Postsynaptic membrane, because the nicotinic receptors being activated or blocked are on the motor end plate.

How does synaptic transmission at the NMJ differ from transmission in the CNS?

NMJ

• motor neuron → skeletal muscle

• ACh

• nicotinic receptors

• produces an EPP

• designed to excite muscle and trigger a muscle AP

CNS

• neuron → neuron

• many different neurotransmitters

• can produce excitation or inhibition

• multiple synaptic inputs are integrated before an AP is generated

What is an excitatory postsynaptic potential (EPSP)?

A graded depolarization of a postsynaptic neuron that moves Vm toward threshold, increasing the probability of an AP.

What major excitatory neurotransmitter does the lecture emphasize in the CNS?

Glutamate, the most widespread excitatory neurotransmitter in the CNS.

What receptors does glutamate activate in the lecture?

Ionotropic:

• AMPA receptors

• NMDA receptors

What ionic currents does glutamate produce?

The lecture emphasizes inward cation currents involving:

• Na⁺

• Ca²⁺

Therefore the slide question asking “Na⁺, Ca²⁺, or both?” is:

Both.

What is an inhibitory postsynaptic potential (IPSP)?

A graded hyperpolarization that moves membrane potential away from threshold, decreasing the probability of an AP.

What is the major inhibitory neurotransmitter emphasized in the CNS?

GABA.

The lecture calls GABA the main inhibitory neurotransmitter in the CNS.

Glycine is also inhibitory.

How can GABA produce an IPSP through GABA-A vs GABA-B receptors?

GABA-A
→ ionotropic
→ directly opens Cl⁻ channels

GABA-B
→ metabotropic/G-protein
→ opens K⁺ channels and closes Ca²⁺ channels

Both reduce postsynaptic excitability.

How do benzodiazepines affect GABA-A receptors?

Benzodiazepines bind GABA-A receptors but do not directly open the Cl⁻ channel.

They enhance/facilitate GABA's action
→ greater inhibitory effect
→ neuronal hyperpolarization
→ reduced AP firing.

What is spatial summation?

Postsynaptic potentials from different synapses/neurons occurring at about the same time add together.

Example:

EPSP from neuron 1 + EPSP from neuron 2
→ larger depolarization
→ may reach threshold.

What is temporal summation?

Repeated impulses from the same presynaptic terminal in rapid succession produce EPSPs that overlap and add together.

If large enough:

→ threshold
→ action potential.

How are excitatory and inhibitory inputs integrated together?

EPSPs and IPSPs combine algebraically.

EPSP → toward threshold

IPSP → away from threshold

So an IPSP can subtract from an EPSP and prevent the postsynaptic neuron from reaching threshold.

What 2 major amino-acid neurotransmitters should you know?

Glutamate = most widespread excitatory CNS neurotransmitter. nonspecific Na/Ca cation channel.
GABA + glycine = inhibitory neurotransmitters. cl- comes into cell.

Glutamate → AMPA/NMDA → Na⁺/Ca²⁺ influx → EPSP.

What catecholamines and indolamine are listed as CNS neurotransmitters?

Catecholamines:

• dopamine

• norepinephrine

• epinephrine

Indolamine:

• serotonin (5-HT)

Serotonin is synthesized from L-tryptophan.

What clinical connections should you know for dopamine?

Loss/deficiency of dopaminergic pathways in substantia nigra region → Parkinson's disease (tremors, trouble initiating movements).

Abnormal dopamine transmission also plays a role in schizophrenia.

The nucleus accumbens receives dopamine input and is involved in reward, motivation, satisfaction, emotion and locomotion.