Synaptic Physiology-L5

Electrical component of synapse

• Current will flow to the next cell with a low resistance through the pathways or gap junctions

Examples of electrical synapses

Cardiac muscle and some smooth muscle

Chemical aspect of a synapse

A neurotransmitter is passed along through the synaptic cleft to the next synapse transmitting a signal

First step of presynaptic neurotransmitter release

An action potential depolarizes the axon terminal

Second step of presynaptic neurotransmitter release

The depolarization opens voltage gated calcium channels and calcium enters the cell

Third step of presynaptic neurotransmitter release

Calcium entry triggers exocytosis of synaptic vesicle contents

Fourth step of presynaptic neurotransmitter release

Neurotransmitter diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell

Fifth step of presynaptic neurotransmitter release

Neurotransmitter binding initiates a response in the post synaptic cell

Post synaptic effects

Postsynaptic receptor proteins bind to receptors and then 1 of 2 things happen

Postsynaptic effects First result

Alter chemical gated ion channels (open or close)

• Inhibitory hyperpolarization

• Excitatory Depolarization

Postsynaptic effects second result

Activate secondary messenger systems

• then one of the four possible effects will take place

effects of postsynaptic communication

1. More sodium in or potassium out → EPSP (Excitatory depolarization)

2. More potassium out Chloride in, or less sodium in → IPSP (inhibitory hyperpolarization)

3. Modifies existing proteins or regulates synthesis of new proteins → coordinated intracellular response

Four possible secondary messengers effects

1. Open specific ion channels on the postsynaptic membrane

2. Activation of cAMP or cGMP

3. Activation of one or more intracellular enzymes

4. Activation of gene transcription

Acetylcholine

Triggers muscle contractions involved in memory, anger and aggression

Norepinephrine

Sympathetic nervous system response

Dopamine

Helps control movement, modulates mood, motivation and reward

GABA

Major inhibitory neurotransmitter, regulation of anxiety

Glutamate

Associated with memory and learning

Serotonin

Regulates mood, body temperature, sleep and appetite

Amines (Neurotransmitter Classes)

Derived from single amino acids

• Dopamine, norepinephrine, e[inephrine

Amino Acids (Neurotransmitter Classes)

• Glutamate

• Aspartate

• Gaba

• Glycine

Peptides (Neurocrines)

Substance P and opioid peptides

Purines (Neurocrines)

AMP and ATP

Gasses (Neurocrines)

NO and CO

Lipids (Neurocrines)

Eicosanoids

What breaks down Ach in the synaptic cleft

Acetylcholinesterase

2 types of Ach Receptors

1. Nicotinic Receptors

2. Muscarinic receptors

Nicotinic Receptors

• found in skeletal muscle

• autonomic ganglia (both CNS and PNS)

Muscarinic receptors

• Different receptor subtypes, All G proteins

• PNS sites

Which receptor does Ach have a higher affinity for?

Equal affinity for both types but agonists and antagonists show selectivity

Catecholamines

• Norepi, epi, dopamine

• Types of enzyme in the cell determines which compound is released

Adrenergic receptors

Both alpha and beta subunits

Alpha 1 is found where

In the blood vessels

Beta 1 receptors are found where

in the heart

Beta 2 receptors are found where

Lungs

Spatial summation

The net sum of inputs spatially on the presynaptic neuron determine the level of excitability

Temporal summation

The net sum of inputs per unit of time on the presynaptic neuron determine the level of excitability

Long term potentiation

• Synapse induces sustained changes in quality or quantity of connections

• May be related to learning or memory

• Glutamate is the key element in potentiation

Steps of long term potentiation

1. Glutamate is released

2. Net sodium entry depolarizes the postsynaptic cell

3. Depolarization ejects magnesium and opens channels for

4. Calcium enters the cytoplasm

5. Cell becomes more sensitive to glutamate

6. Paracrine from postsynaptic cell enhances glutamate release

Fatigue of synaptic transmission

• Exhaustion of the stores of transmitter in the synaptic terminals

• Causes areas of the nervous system to lose excitability after a while

• Development of fatigue is a protective mechanism against excess neuronal activity

Effects of acidosis on synaptic transmission

• Depresses neuronal activity

• pH change from 7.4 to 7.0 usually will induce coma

Effect of alkalosis on synaptic transmission

• Increase in neuronal excitability

• pH change from

Effect of hypoxia on synaptic transmission

• Brain is highly dependent on oxygen

• No other access to alternative energy sources

• No ATP for pumps because no oxygen

• Interruption of brain flow for 3-7 seconds can lead to unconsciousness