6- Synapses

Synapse

site where information is transmitted from one cell to another

Electrical synapse

allow current to flow from one excitable cell to the next through gap junctions

Gap junctions

low resistance pathways between cells; found in cardiac muscle and different types of smooth muscle

Chemical synapse

information is transmitted from one excitable cell to another via a neurotransmitter

Neurotransmitter

a substance released from the presynaptic terminal of the sending cell that binds to receptors on the postsynaptic terminal on the receiving cell

Synaptic cleft

a gap between the presynaptic cell membrane of the sending cell and the postsynaptic cell membrane of the receiving cell

What happens when a presynaptic cell action potential occurs?

Ca2+ channels open.

What causes synaptic vesicles to be released into the synaptic cleft?

Influx of Ca2+ into the presynaptic terminal.

How do neurotransmitters reach the postsynaptic membrane?

They diffuse across the synaptic cleft.

What are the two possible effects of neurotransmitter binding on the postsynaptic cell?

Excitatory (depolarization) or Inhibitory (hyperpolarization).

What is the directionality of chemical synapse neurotransmission?

Unidirectional.

What is synaptic delay?

The time required for chemical neurotransmission to occur.

One-to-one synapses

Single presynaptic cell action potential causes a single postsynaptic cell action potential

-Neuromuscular juction

One-to-many synapses

Single presynaptic cell action potential causes a burst of action potentials in multiple postsynaptic cells

-Uncommon; causes activity amplification

Many-to-one synapses

Many presynaptic cell action potentials converge on a single postsynaptic cell

-AP inputs summate; quantity of inputs determines if the postsynaptic cell with fire AP

What are excitatory postsynaptic potentials (EPSPs)?

Synaptic inputs that depolarize the postsynaptic cell and bring it closer to the AP threshold.

What ion channels are involved in producing EPSPs?

Opening Na+ and K+ channels.

Which neurotransmitters are considered excitatory?

Acetylcholine, norepinephrine, epinephrine, dopamine, glutamate, and serotonin.

How are EPSPs similar to nicotinic ACh receptors?

Both involve the opening of ion channels that lead to depolarization.

What is an inhibitory postsynaptic potential (IPSP)?

Synaptic inputs that hyperpolarize the postsynaptic cell and move it away from the AP threshold.

What ion channels are opened to produce an IPSP?

Cl- channels.

What are some inhibitory neurotransmitters?

y-aminobutyric acid (GABA), glycine, and nitric oxide.

Presynaptic cell terminals converge on a single postsynaptic cell to relay

excitatory or inhibitory signals

Synapse presynaptic information may be integrated either

spatially or temporally

Spatial summation

Occurs when two or more presynaptic inputs arrive at the postsynaptic cell simultaneously

-If both are excitatory, they will combine to produce greater depolarization than if they were alone

-If one excitatory and the other is inhibitory, they will cancel each other out

Temporal summation

Occurs when two presynaptic inputs arrive at the postsynaptic cell in rapid succession

-Because the inputs overlap in time, they summate

What is facilitation in synaptic activity?

Response to brief increases in the frequency of nerve stimulation.

What is augmentation in synaptic activity?

Increased synaptic vessel release; increases nerve plasticity.

What is potentiation in synaptic activity?

Increased release of neurotransmitters into the synapse; also known as long-term potentiation.

What is synaptic fatigue?

Repeated nerve stimulation produces a smaller than expected response.

Motor neuron

nerves that innervate muscle fibers

motor unit

a single moto neuron and the muscle fibers it innervates

How many muscle fibers can one motor neuron innervate?

One motor neuron may innervate a few muscle fibers or thousands.

What type of motor units are used for fine motor activities?

Small motor units are used for fine motor activities (e.g., facial expressions).

What type of motor units are used for gross muscular activities?

Large motor units are used for gross muscular activities (e.g., lifting weights).

Neuromuscular junction

synapse between a motor neuron and a muscle fiber

What happens to action potentials in neuromuscular transmission?

Action potentials are propagated down the motor neuron.

How do local currents affect the motor neuron during neuromuscular transmission?

Local currents depolarize each adjacent region to the action potential threshold.

What occurs when the presynaptic nerve terminal is depolarized?

Voltage-gated Ca2+ channels in the presynaptic membrane open.

What happens to Ca2+ permeability in the presynaptic nerve terminal?

Presynaptic nerve terminal Ca2+ permeability increases.

-Ca2+ flows into the terminal down its electrochemical gradient

What occurs when Ca2+ flows into the presynaptic nerve terminal?

Ca2+ causes the release of acetylcholine (Ach) from presynaptic vesicles.

How do vesicles release acetylcholine in neuromuscular transmission?

Vesicles fuse with the plasma membrane and empty their contents into the synaptic cleft by exocytosis.

What is the role of the motor end plate in neuromuscular transmission?

The motor end plate contains nicotinic receptors for acetylcholine.

What happens to neurotransmitters during neuromuscular transmission?

Neurotransmitters diffuse across the synaptic cleft.

What is the nicotinic receptor?

A ligand-gated ion channel that also functions as a Na+/K+ channel.

How many molecules of ACh bind to the nicotinic receptor?

Two molecules of ACh bind to the α subunits.

What happens when ACh binds to the nicotinic receptor?

It causes a conformational change that increases the permeability of both Na+ and K+.

What drives the motor end plate potential (EPP) to its equilibrium potential?

Na+/K+ electrochemical gradients

What direction does Na+ move during the motor end plate potential?

Na+ moves into the cell

What direction does K+ move during the motor end plate potential?

K+ moves out of the cell

To what voltage does the EPP depolarize?

-50 mV

Is the EPP an action potential?

No, the EPP is just a local depolarization of the motor end plate

What is a Miniature Endplate Potential (MEPP)?

The smallest possible change in motor end plate membrane potential caused by the content of a single synaptic vesicle.

What do MEPPs summate to form?

An Endplate Potential (EPP).

How much does a MEPP depolarize the motor end plate?

By 0.4 mV.

How many MEPPs are required to form an EPP?

100 MEPPs.

By how much does an EPP depolarize the end plate?

By 40 mV.

What is the resting potential of the motor end plate?

-90 mV.

What is the threshold potential of the motor end plate?

-50 mV.

How does motor end plate depolarization spread to adjacent muscle fibers?

by local currents

-Adjacent fibers are depolarized and fire action potentials that propagate down the muscle fiber

What enzyme degrades acetylcholine (ACh) at the motor end plate?

Acetylcholinesterase (AChE)

What is the result of acetylcholinesterase (AChE) activity at the motor end plate?

It terminates the end plate potential (EPP).

What percentage of choline is returned to the presynaptic terminal for recycling?

Approximately 50%

What mechanism is used to transport choline back to the presynaptic terminal?

Na+ -choline cotransport

What is the function of Botulinum toxin?

Blocks release of ACh from presynaptic terminals

What is the mechanism of action of Curare?

Competes with ACh for nicotinic receptor α subunit binding

What do AChE inhibitors do?

Prevent degradation of ACh in the synaptic cleft

-Also called anticholinesterases (neostigmine)

What condition is treated with AChE inhibitors?

Myasthenia gravis

What is the function of Hemicholinium?

Blocks choline reuptake into presynaptic terminals

Myasthenia gravis

neuromuscular disorder characterized by gradually increasing profound muscle weakness

-Drooping of the eyelid is the first symptom

-Patients may develop diplopia

Tetanus

neuromuscular disorder that Creates rigid paralysis; Any minor stimulus causes major muscle spams

-Caused by tetanospasmin toxin (from C. tetani bacteria)

What is the first criterion for a substance to be classified as a neurotransmitter?

Must be synthesized in the presynaptic cell

What is the second criterion for a substance to be classified as a neurotransmitter?

Must be released by the presynaptic cell on stimulation

What is the third criterion for a substance to be classified as a neurotransmitter?

If applied exogenously to the postsynaptic membrane at physiologic concentration, the response must mimic the in vivo response

Neurotransmitter categories

-Choline Esters

-Biogenic Amines

-Amino Acids

-Neuropeptides

What are common neurotransmitters?

Common neurotransmitters include adrenaline, GABA, noradrenaline, acetylcholine, dopamine, glutamate, serotonin, and endorphins.

What is the role of adrenaline?

Adrenaline is produced in stressful situations and increases heart rate and blood flow, leading to a physical boost and heightened awareness.

What is the function of GABA?

GABA calms firing nerves in the central nervous system. High levels improve focus, while low levels can cause anxiety. It also contributes to motor control and vision.

What does noradrenaline affect?

Noradrenaline affects attention and responding actions in the brain and contracts blood vessels, increasing blood flow.

What is the role of acetylcholine?

Acetylcholine is involved in thought, learning, and memory. It activates muscle action in the body and is associated with attention and awakening.

What is dopamine associated with?

Dopamine is associated with feelings of pleasure, addiction, movement, and motivation. People tend to repeat behaviors that lead to dopamine release.

What is glutamate's primary function?

Glutamate is the most common neurotransmitter and is involved in learning and memory, regulating the development and creation of nerve contacts.

What does serotonin contribute to?

Serotonin contributes to well-being and happiness, helps regulate the sleep cycle, and aids in digestive system regulation. It is affected by exercise and light exposure.

What are endorphins released during?

Endorphins are released during exercise, excitement, and sex, producing feelings of well-being and euphoria while reducing pain.

What is acetylcholine formed from?

Acetylcholine is formed from acetyl coenzyme A (acetyl CoA) and choline.

What enzyme is responsible for the formation of acetylcholine?

Choline acetyltransferase.

Where is acetylcholine stored?

In synaptic vesicles with ATP and proteoglycan.

What is the only neurotransmitter used at the neuromuscular junction?

Acetylcholine.

From which neurons is acetylcholine released in the parasympathetic nervous system?

From all preganglionic and most postganglionic neurons.

From which neurons is acetylcholine released in the sympathetic nervous system?

From all preganglionic neurons.

From which neurons is acetylcholine released in the adrenal medulla?

From presynaptic neurons.

How is acetylcholine recycled?

By acetylcholinesterase (AChE).

What happens to approximately half of the choline broken down by AChE?

It is taken back into the presynaptic terminal and reformed into acetylcholine.

What are biogenic amines?

Biogenic amines are organic compounds that play important roles in neurotransmission and include norepinephrine, epinephrine, dopamine, serotonin, and histamine.

What is the common precursor for norepinephrine, epinephrine, and dopamine?

Tyrosine

What is the first step in the biosynthetic pathway of dopamine?

Tyrosine is converted to L-dopa.

What enzyme converts dopamine to norepinephrine?

β-hydroxylase

What enzyme converts norepinephrine to epinephrine?

Phenylethanolamine-N-methyltransferase (PMNT)

What do dopaminergic neurons secrete?

Dopamine

What do adrenergic neurons secrete?

Norepinephrine