Ligand-Gated Ion Channels Flashcards
What is a receptor superfamily?
A group of receptors with a similar basic molecular structure and that use the same signal transduction pathway
List the major receptor superfamilies
- LGICs
- GPCRs
- Kinase-linked receptors
- Nuclear receptors (extracellular)
What is a LGIC?
Diverse superfamily of multimeric integral membrane proteins that incorporate extracellular ligand- binding sites & a central transmembrane ion-permeable channel/pore
When an ion flows through the activated channel what happens?
Modulation of cellular function
LGICs involved in a wide range of biological functions, give examples
- Synaptic transmission & neural communication
- Cell excitation
- Muscle contraction & intracellular signalling
(Excitatory) Mediate influx of cations causes membrane ____
depolarisation
(Inhibitory) Mediate influx of anions causes membrane ____
hyperpolarisation
List the receptor classification of LGIC based on mol structure & subunit stoichiometry
- Cys-loop receptor family (pentameric - 5 subunits) e.g. nAChR
- Ionotropic glutamate receptor family (tetrameric - 4 subunits)
- P2X receptor family (trimeric - 3 subunits)
Cys-loop receptors arranged around a _______ _________
central ion conducting pore
Ionotropic are _______
non-selective cation channels gated by glutamate
P2X are ________
non-selective cation channels gated by extracellular ATP
Cys-loop LGIC activated by neurotransmitter _____ and also by ____
acetylcholine
nicotine, hence AChR
Binding of ACh, influx of ____ then membrane depolarisation, influx of ____ & neurotransmitter release
Na + ions
Ca 2+
List the nicotine acetylcholine receptors
- Muscle (Nm) subtype (occur at NMJ)
- Neuronal (Nn) subtype (occur at autonomic ganglia in CNS)
Where are the 2 ACh binding sites
- At the interface between the two a subunits and neighbouring y/e subunits
Autonomic nervous system
- Nm mediates fast excitatory synaptic transmission >
- Nn mediates same & autonomic control of peripheral organs
- skeletal muscle contraction
GABAA receptors activated by amino acid transmitter ____
y-aminobutyric acid (GABA)
Binding of GABA > channel opening > influx of Cl- ions > membrane ______, ____ post-synaptic transmission
hyperpolarisation
fast
Where do GABAA receptors occur
in CNS, post synaptic inhibition of neuronal activity
GABA binding sites located at ______
a/B subunit interfaces
Where do synaptic receptors occur?
At synaptic sites within the synaptic cleft
What are synaptic receptors activated by?
GABA & mediate phasic inhibition
Lower affinity for GABA & high benzo sensitivity
Where do extrasynaptic receptors occur?
Outside synaptic sites
What are extrasynaptic receptors activated by?
GABA spillover & mediate tonic inihibition
Higher affinity for GABA & low benzo sensitivity
GABA have a widespread distribution in the _____
brain
GABA drug examples
benzodiazepines, alcohol, general anaesthetics
GABA receptors bind to _____ binding sites
allosteric
positive allosteric modulation
Effect is reflected as increased frequency & opening of the receptor _____ ion channel
Cl-
