Chemistry and physiology of the synapse Flashcards
ACh on the heart
mAChR –>
G-protein –>
K+ channel –> hyperpolarisation
ACh on skeletal muscle
nAChR –>
Na+ channel –>
Depolarisation
Ligand gated ion channels
Responsible for fast transmission of information to the postsynaptic neuon
Ionotropic receptors
Opened by ligand binding rather than voltage change
Ligand= neurotransmitter
Allows influx of ions through central pore
Fast synaptic transmission: glutamate
Flux Na+
Excitatory post synaptic potential
Depolarises postsynaptic neurone
Threshold met causes action potential
Fast synaptic transmission: GABA
Flux Cl-
Inhibitory post synaptic potential
Hyperopolarises postsynaptic neurone
Inhibits neurone firing unless sufficient glutamate to counteract
Nicotinic
Most well studied ionotropic receptors
Activation by ACh causes excitation and contraction of muscle cells
Three types of glutamate receptors
NMDA
AMPA
Kainate
Names based on the agonists selective for them
NMDA receptors
Agonist: NMDA
Antagonist: APV
AMPA rececptors
Agonist: AMPA
Antagonist: CNQX
Kainate receptors
Agonist: kainic acid
Antagonist: CNQX
No-NMDA receptors
Fast opening channels permeable to Na+ and K+
Responsible for early phase of EPSP
NMDA receptor
Slow opening channel permeable to Ca2+, Na+ and K+
Requires extracellular glycine as cofactor to open the channel
Gated by membrane voltage
- Mg2+ plugs pore at resting potential
- membrane depolarises so Mg2+ ejected allowing conductance
Responsible for late phase ESPS
NMDA receptors- regulation of channel opening
Influx of Ca2+ as well as Na+ leads to activation of a number of enzymes and other cellular events
Cause widespread changes to postsynaptic cell
Action of NDMA receptors and resultant neuroplasticity may be molecular mechanisms that leads to long term memory formation
NMDA receptors and schizophrenia
NDMA receptors also inhibited by phencyclidine and MN801
Both bind in the open pore
Blockade produces symptoms that resemble hallucinations associated with schizophrenia
Glutamate excitotoxicity
Excessive Ca2+ influx into cell activates calcium dependent enzymes that degrade proteins, lipids and nucleic acids
Occurs after cardiac arrest, stroke, oxygen deficiency and repeated intense seizures
Glutamate
Excitatory
GABA
Inhibitory
brain
Glycine
Inhibitory
spinal cord and brain stem
Nicotine
Excitatory at NMJ
Excitatory or modulatory in CNS
Serotonin
Excitatory or modulatory
ATP
Excitatory
Metabotropic receptors
Transduce signals into cell not directly though an ion channel but through G-protein which triggers series of intracellular events
GPCR
Seven transmembrane domain protein
Transmitter binds to extracellular domain
Binding triggers uncoupling of heteromeric G protein on intracellular surface
Transduces signal across cell membrane