Synaptic transmission

Types of synaptic connections

• Chemical
• Electric
• Conjoint
 Electric synapse
• Gap junction - Cylinder of 6 connexin subunits
• Ions just flow through the channel and change the
potential of the cell
• Regulation of the ion flow:
– c Ca2+, pH, cAMP
• Connection between:
– glial cells and neurons
– rods and cones
• Advantage: transmission is faster
 Chemical synapse
• The most common type in humans and
vertebratea
• Adavantages:
– Polarity
– Integration
– Modulation
 Chemical synpse
• Polarity:
– The transmission succeds only in one direction
• Integration:
– There are lots of synaptic clefts on one neuron and
incoming signals are summated before generating the
action potential
• Modulation:
– The transmission can be influenced by other chemicals
in the synaptic cleft
Electric and chemical synapse
 Main neurotransmitters in human
body
• Acetylcholine
• Catecholamines
– Dopamine, noradrenaline, adrenaline
• Serotonine
• Histamine
• GABA, glycine – inhibiting
• Glutamate, aspartate - excitating
 Acetylcholine
• The parasympathetic nervous system
• acetylcholinesterase:
– Brokes the acetylcholine down in the synaptic
cleft after binding to the receptor
– Acetylcholine → acetate + choline
• Cholin reuptake to the presynaptic neuron
• M receptors - G-protein + ion channel
• N receptors - part of Cl- channel
 Acetylcholine
• N-receptors
– heteroreceptors of glutamatergic,
hydroxytryptaminergic, GABAergic or
dopaminergic neurons
– Increase of released neurotransmitter

• learning, memory, motoric functions

 Acetylcholinesterase inhibitors
• Acetylcholine stays longer in the synaptic
cleft, works longer

• They are used to treat Alzheimer´s disease:

– Physostigmine, rivastigmine, donepezile,
galantamine
 Atropine

• M and N receptors antagonist, is used as

active substance in
– Spasmolytic drugs – cramps of GIT
– Mydriatic drugs
– Prevents bardycardia
 Catecholamines
• Adrenaline

• Noradrenaline

• Dopamine
 Catecholamines

• Reuptake from synaptic cleft

• MonoAaminoOxidase-A (MAO-A):
– breaks down adrenaline and noradrenaline in
the neurons
• MAO-B: breaks down dopamine in
extracellular space
• Cresyl-O-MethylTransferase (COMT)
 Dopamine
• Receptors – adenylatcyklase
– D1+5 - stimulation
– D2,3,4 - inhibition

• D2 - motoric functions
• D3,4 - limbic system
• D4 - in GABAergic neurons
• Adrenaline and noradrenaline are agonists
 Parkinson´s disease

• Deficit of dopamine in the neurones of

basal ganglia

• Treatment:
– COMT inhibitors: tolcapone , entacapone
– Selective MAO-B inhibitors: selegiline
 Adrenaline, Noradrenaline
• The sympathetic nervous system
• Receptors with G-protein – α, β
• Disorders in adrenergic neurotransmission:
– Narcolepsia
– Concentration disorders
– Depression
– Eating disorders
 Adrenaline, Noradrenaline
• Abused drugs:
– Psychostimulants- noradrenaline, dopamine and
hydroxytryptamine synaptic output stimulation
• Amfetamine, pervitine, MDMA - extasy
• Antidepressants
– noradrenaline, dopamine and
hydroxytryptamine reuptake inhibitors
– Inhibitors of MAO
 Serotonine
(5-hydroxytryptamine)

• Reuptake from synaptic cleft

• MAO-A
• Receptors 5-HydroxyTryptamine1-7 (5-HT),
second-messenger systems
• Activation of the 5-HT receptors
– hypoactivity (sedation, sleep, depression)
– agressivity, anxiety, sexuality, eating
– headache
 Histamine
• Receptors: G-protein
– H1: excitating, hypothalamus, PNS
– H2: inhibiting, Hippocampus, Cortex
– H3: histamine synthesis and output
– Heteroreceptors: inhibition of acetylcholine,
dopamine, noradrenaline and hydroxytryptamine
output
• Regulation of sleep and vigilance
• Regulation of Eating and water uptake
 Antipsychotics

• H1-antihistaminergic side effects:

– Somnolence
– Increase of body weight
 Antihistaminics

• H1: prevention of alergic reactions,

sedatives, antiemetics, antivertiginous
• H2: inhibition of gastric HCl secretion
• H3: experimental research
 γ-Amino Butyric Acid
• Main inhibiting neurotransmitter in vertebratea
• Reuptake from synaptic cleft
• GABA A receptor
– part of receptor for: alcohol, benzodiazepines,
barbiturates
– regulation of Cl- channel
• GABAB receptor – G-protein, inhibition of other
neurotransmitters output
 Glycin
• Inhibiting neurotransmitter
• Reuptake from synaptic cleft
• Receptors- Cl- channels
• Strychnin – agonist - cramps
 Glutamate, Aspartate
• Ionotropic receptors: Na+, Ca2+, K+ channels
– NMDA
– AMPA
– kainate
• Metabotropic receptors: G-protein
– mGLUR 1-8
• Memory functions
 Glutamate, Aspartate

• Antiepileptics
– Topiramate: AMPA inhibitor
• General anestetics
– Ketamine: NMDA antagonist