Transmission in CNS Flashcards
Structure of a neuron?
- dendrites (inout region)
- cell body (nucleus that stores DNA, protein synethsis etc)
- axon (main conduction unit, carries signals in action potential form)
- axon terminals (output region, neurotransmitter release)
What types of synaptic transmission are there?
Electrical or chemical (most are chemical)
What is the name of the gap between cells at a synapse?
Synaptic cleft
What is action potential?
depolarisation of the axon membrane in order to signal
action potential opens calcium ion channels at the presynaptic terminal to initiate the neurotransmitter process
What are the stages of an action potential?
- resting membrane potential around -70mV
- sodium channels open: depolarisation (approx + 30mV)
- sodium channels close
- potassium channels open - repolarisation
- potassium channels close on hyperpolarisation
- return to resting potential
What are the main things that happen at the synapse?
- synthesis
- storage
- release
- inactivation/reuptake
How is acetylcholine synthesised?
Acetyl Coenzyme A + choline, catalysed by choline acetyltransferase to produce acetylcholine and CoemzymeA
always in excess so enzyme is not saturated
What neurones is Choline acetyltransferase specific to?
Cholinergic ones
Where is acetylcholine stored?
in synaptic vesicles in the axonal membrane
How is acetylcholine released?
Arrival of action potential at axonal terminal causes a calcium ion influx, which triggers release of the vesicle contents
Which receptors does acetylcholine bind to?
Muscarinic (M1-5) and nicotinic
Structure of nicotinic receptors?
5 subunits
- alpha (1-10)
- beta (B2-B5)
- delta
- epsilon
- gamma
different combinations in different types of receptor
What are the two main types of nicotinic receptor?
Muscular and neuronal
Location and structure of muscular nicotinic receptors?
neuromusclar junctions
ααβεδ ligand gated ion channel
Location and structure of neuronal nicotinic receptors?
Autonomic ganglia, CNS
Various αβ subunits E.g. neuronal nicotinic receptor
- α4β2 and the α7 subtypes
Inactivation and reuptake of acetylcholine?
acteylcholine esterase breaks down into acetateion and choline
40-50% of the choline formed is taken back up into the presynaptic cell by a transporter specific to cholinergic cells
What is a neuromuscular junction?
chemical synapse between a motor neurone and skeletal muscle
How does acetylcholine induce a response in the post synaptic cell?
ligand gated ion channels - so allow infux of sodium ions and depolarisation to continue the action potential
How does depolarisation affect the muscle cell at the neuromuscular junction?
depolarisation triggers calcium ion entry into the muscle cell which causes contraction
What is myasthenia gravis?
autoimmune condition. produce antibodies that block or damage the acetylcholine receptors which prevents the muscle contracting
Which muscles are predominantly affected by myasthenia gravis?
facial muscles and those that control swallowing
What medications can be used for myasthenia gravis?
Pyridostigmine - prevent breakdown of acetylcholine (work best in mild cases)
How is dopamine synthesised?
- l-tyrosine to l-dopa by tyrosine hyroxylase
- l-dopa to dopamine by dopa decarboxylase
tyrosine hyroxylase is rate determining step
Where is dopamine stored?
in synaptic vesicles at the axonal terminal, released when action potential triggers influx of Calcium ions
Which receptors does dopamine bind to?
D1 family (D1 and D5) - excitatory D2 family (D2, 3, 4) - inhibitory
How is dopamine deactivated?
Metabolised by two enzymes:
- Catechol-O-methyltransferase (COMT)
- Monoamine oxidase (MAO)
How does reuptake of dopamine occur?
Catecholamines have highly specific active transport mechanisms to remove transmitter from synapse into presynaptic terminal
Dopamine Transporter - DAT
What are the 4 dopamine pathways?
Nigrostriatal
Mesolimbic
Mesocortical
Tuberoinfundibular
What does the nigrostriatal pathway control?
Substantia nigrata to caudate and putamen (striatum)
Dorsal striatum: motor function (Parkinson’s)
Associative striatum: learning, habituation, memory, attention, motivation, emotion, volition
antipsychotics can decrease dopamine and cause parkinsonism
What does the mesolimbic pathway control?
Vetral Tegmented Area (VTA) in midbrain to limbic regions associated with rewards, motivation, affect and memory
includes ventral striatum (nucleus accumbens), amygdala, hippocampus and medial frontal cortex
too much dopamine in this pathway leads to positive symptoms (hallucinations etc)
What is the mesocortical pathway?
VTA to frontal cortex (including dorsolateral prefrontal cortex). controls cognitive function, motivation and emotional resposne
too little dopamine in this pathway in schizophrenia leads to negative symptoms
What is the tuberoinfundibular pathway?
Tuberal region to median eminence (infundibular region at top of pituitary stalk)
inhibits prolactin release from pituitary (inverse relationship between dopamine and prolactin)
What does an agonist do at a receptor?
stimulate the receptor and mimic the natural ligand
What does an antagonist do at a receptor?
block the receptor and stop the effects of the natural ligand
What does a partial agonist do at a receptor?
unable to induce maximal activation of a receptor, regardless of the amount
What are some of the main types of receptor?
Ionotropic Receptors
Metabotropic Receptors
Kinase-linked Receptors
Intracellular Receptors
What are ionotropic receptors?
part of a ligand gated ion channel protein - activation causes changes in ion conductance
opened by neurotransmitters to allow passage of sodium ions (excitatory) or potassium or chloride ions (inhibitory)
examples: some receptors for acetylcholine, glutamate, and GABA
What are metabotropic receptors?
A receptor protein in the membrane, coupled to an effector via G proteins. a conformational change in the G protein activates enzymes needed for the effect
Speed of response of ionotropic receptors?
msecs, used in fast neurotransmission.
Speed of response of metabotropic receptors?
secs/mins/hours. used for slower neurotransmission processes (hormone, growth factors)
Speed of response of kinase receptors?
mins/hours
Speed of response of instracellular receptors?
long-lasting
How can the acetylcholine sysnthesis pathway be targeted by drugs?
Choline concentration determines rate, so increasing or restricting choline will increase or decrease
What type of drugs are used to treat schizophrenia?
antipsychotics: D2 receptor agonists
What type of drugs are used to treat parkinsons?
Dopaminergic drugs (precursors/agonists)
What type of drugs are used to treat Alzheimer’s?
- Acetylcholinesterase inhibitors
- NMDA receptor antagonist
What kind of drugs are used to treat epilepsy?
GABA/glutamate transmission (anticonvulsants)
What kind of drugs are used to treat depression?
SSRIs
What is Parkinson’s disease?
Loss of dopamine in the nigrostriatal pathway, diminished in the striatum. Dopamine’s precursor (L-DOPA) is an effective treatment
