K1vii: Topic: Major neurotransmitters & their role

Definition

  • Neurotransmitter = a chemical agent released by a neuron which transfers an impulse to neighbouring neurons/cells
  • NT Criteria
    • Synthesised by neuron
    • Stored in nerve terminal
    • Released in sufficient [ ] to affect postsynaptic cell
    • Mechanism for removal

Synaptic Transmission

  1. Synthesis: of NT molecule from precursors
  2.  Storage: of NT molecules into vesicles
  3.  Release: AP causes Ca2+ influx → vesicles fuse with membrane → NT molecules released
  4.  Binding: NT activates post synaptic receptor → INHIBITORY/EXCITATORY RESPONSE
    • INHIBITORY POST SYNAPTIC POTENTIAL (IPSP) makes it more difficult for post synaptic neuron to generate AP
    • EXCITATORY POST SYNAPTIC POTENTIAL (EPSP) makes it easier for post synaptic neuron to generate AP
  5.  Removal: via reuptake/metabolism

Classification of Neurotransmitters

  • Amino acids e. glutamine, GABA, glycine
  • Biogenic amides
    • From decarboxylation of amino acids
    • e. Adrenaline, NA, dopamine, histamine

↓ further subdivides

    • EXCITATORY: NMDA, nACh → membrane depolarisers
    • INHIBITORY: GABA → membrane hyperpolarisation

Classificaiton of Neurotransmitter Receptors

Ionotropic (direct)

  • A membrane protein
  • Made of subunits
  • Allows passage of an ion

Metabrotropic (indirect)

  • Transmitter binds to a GPCR
  • Activates 2nd messenger pathways

FOR EXAMPLE – Cholinergic

nAChR → Excitatory Ionotropic

  • 5 subunit receptor
  • Central ion pore
  • ACh binds 2 α subunits
  • Opens pore
  • Na+ influx/small Ca2+ influx/K+ outflux
  • Depolarisation
  • Propagation of AP across NMJ

mAChR → Inhibitory & Excitatory Metabrotropic

  • 7 transmembrane domains
  • GPCR
  • M1 (parietal cells)
    • Phospholipase C activation
    • ↑DAG/IP3
    • ↓K+ conductance
    • Membrane depol
  • M2 (PM cells)
    • ↓AC
    • ↑K+ conductance
    • Membrane hyperpolarisation
    • ↑time to depol
    • ↓HR

FOR EXAMPLE – Adrenergic = ALL metabrotopic

α Receptors

  • α1
    • ↑Phospholipase C
    • ↑IP3/DAG
    • ↑Ca2+
    • Depol
    • VC (excitatory)
  • α2
    • ↓AC
    • ↓cAMP
    • ↓Ca2+
    • ↓NA release presynaptically (inhibitory)
  • β receptors:
    • ↑AC
    • ↑cAMP
    • ↑Ca2+ (excitatory)

β1 = ↑FoC, ↑HR

β2 = VD, bronchodilation

β3 = brown fat lipolysis

 

NT

Glutamate

(amino acid)

Action

1° excitatory NT

Synthesis

From ketoglutamate (Krebs)

Secretion

CNS – brain & SC

Receptors

Ionotropic

3 types

  1. NMDA
  2. AMPA
  3. Kainate

Uptake/Metabolism

Active transport back into neurons

NT

GABA

(amino acid)

Action

1° inhibitory NT

Synthesis

From glutamate

Secretion

CNS – SC, brain

Receptors

GABAA ionotropic

Uptake/Metabolism

GABA transaminase & reuptake

NT

Glycine

(amino acid)

Action

Excitatory & inhibitory

Synthesis

–

Secretion

CNS

Receptors

Ionotropic

Uptake/Metabolism

– 

NT

Dopamine

(biogenic amine)

Action

Excitatory & inhibitory (i.e. inhibits NA release = VD)

Synthesis

From tyrosine

Secretion

CNS

PNS

Receptors

GPCR metabrotropic

Uptake/Metabolism

Metabolism by COMT/MAO

NT

NA

(biogenic amine)

Action

Excitatory & inhibitory

Synthesis

From tyrosine

Secretion

CNS

PNS

Receptors

GPCR metabrotropic

Uptake/Metabolism

Metabolism by COMT & MAO

NT

Adrenaline

(biogenic amine)

Action

Excitatory & inhibitory

Synthesis

From tyrosine

Secretion

CNS

PNS

Receptors

GPCR metabrotropic

Uptake/Metabolism

Metabolism by COMT/MAO

NT

Serotonin

(biogenic amine)

Action

Excitatory & inhibitory

Synthesis

From tryptophan

Secretion

CNS

Receptors

Ionotropic & metabrotropic

Uptake/Metabolism

Reuptake & MAO

NT

Histamine

(biogenic amine)

Action

Multiple actions

Synthesis

From histidine

Secretion

CNS

Receptors

–

Uptake/Metabolism

–

NT

ACh

(no category)

Action

Main NT of PNS

Synthesis

From choline + Acetyl CoA

Secretion

PNS

Receptors

Nicotinic – ionotropic

Muscarinic metabrotropic

Uptake/Metabolism

ACh-ase