Chemical Transmission in the Nervous System Flashcards
Action potentials are propagated down the neuron by the opening of
Na+ channels
tf these are a target for blocking NT release
How is excitation targeted pharmacologically at synapses?
blocking of Na+ channels prevents AP propogation and tf NT release
How is NT synthesis targeted pharmacologically at synapses?
targeting enzymes that produce NT
provide substrate or block activity
How is NT storage targeted pharmacologically at synapses?
vesicle storage and release
How is NT metabolism targeted pharmacologically at synapses?
enzymes that degrade NT
How is NT release targeted pharmacologically at synapses?
fusion of vesicles with membrane to release contents into synaptic cleft
How is NT degradation targeted pharmacologically at synapses?
enzymes that degrade NT; reuptake of NT by pre or post-synaptic membranes
How are receptors targeted pharmacologically at synapses?
agonists or antagonists for NT receptors; prejunctional receptors can alter NT release (e.g. a2-aR limits NA release)
The somatic nervous system is ________ and innervates
voluntary
skeletal muscle and overlying skin
the parasympathetic nervous system is _______ and innervates
involuntary (ANS)
heart, glands, and smooth muscle
the sympathetic nervous system is _______ and innervates
involuntary (ANS)
heart, blood vessels, glands (including sweat, adrenal)
What is unique about the SNS innervation at the adrenal gland?
it releases ACh rather than NA to stimulate adrenaline release
What are the two main chemical neurotransmitters of the peripheral nervous system?
ACh and NA
How is ACh synthesized?
- choline receptor on neurons transports dietary choline
- acetyl-CoA from mitochondria via choline acetyltransferase –> ACh
- ACh transported into vesicles via a carrier
- drugs can modulate synthesis and storage but are of limited clinical use
How is NA synthesized?
- tyrosine –> neurons via transporter
- broken down by tyrosine hydroxylase –> L-DOPA (L-dihydroxyphenylalanine)
- broken down into dopamine by DOPA decarboxylase
- dopamine can be the terminal product, or
- broken down by dopanine beta-hydroxylase to NA in synaptic vesicles
-
synthesis and storage can be modulated by drugs
- L-DOPA precursor drug can +dopamine production
- enzyme blockers can -dopamine and tf -NA synthesis
How is adrenaline synthesized?
- in adrenals, NA is converted to adrenaline
- via PNMT (phenylethanolamine-N-methyl transferase) in secratory vesicles
What is the anatomical configuration of the ANS?
two fibres:
pre-ganglionic fibres from the CNS
post-ganglionic fibres from the autonomic ganglia
What is the anatomical configuration of the somatic NS?
one fibre
CNS to skeletal muscle (alpha motor neuron)
What is the anatomical structure of the sympathetic nervous system?
- short pre-ganglionic fibres
- ganglia located in sympathetic chain near SC
- long post-ganglionic fibres
- integration and modulation of responses
What is the anatomical structure of the parasympathetic nervous system?
- long pre-ganglionic fibres
- short post-ganglionic fibres
- ganglia close to tissue, sometimes within
What are co-transmitters?
- released with the dominant NTs ACh and NA from ANS neurons
- e.g. ATP in sympathetic nerves releasing NA can act on purine receptors to fine-tune responses downstream
How is ACh inactivated?
- by degredation to prevent constant activation of post-synaptic receptors
- degraded by acetylcholinesterase anchored to the post-junctional membrane
- some ACh binds to cholinergic receptors and acitvates the post-synaptic membrane
- other ACh binds AChE for degradation
- tf degradation can be modulated by drugs
How is NA inactivated?
- by uptake
- taken back into the releasing neuron (high-affinity uptake 1)
- repackaged for subsequent signalling episodes
- taken into post-synaptic neuron/tissue (low-affinity uptake 2)
What is the neurotransmitter of the somatic nervous system?
ACh
released by upper motor neurons onto nicotinic receptors of the alpha motor neurons
alpha motor neurons relay stimulus by releasing ACh onto nicotinic receptors of muscles
causes excitation
What is the main neurotransmitter of the PSNS?
ACh
preganglionic nerves release ACh onto nicotinic receptors at the ganglion
acts on nicotinic receptors of postganglion neurons
postganglionic neurons then release ACh on muscarinic receptors
What is the main neurotransmitter of the sympathetic nervous system?
noradrenaline and adrenaline*
preganglionic to postganglionic is ACh acting on nicotinic receptors
postganglionic nerves synapse via adrenergic receptors using NA or A*
*except at sweat and adrenal glands where ACh is used
What is the neurotransmitter of ganglionic transmission?
ACh
ACh acts on (receptors)?
- Nicotinic receptors (ligand-gated ion-channel)
- ANS preganglionic synapse & Somatic postganglionic synapse
- Muscarinic receptors (GPCR)
- PSNS postganglionic synapse
NA acts on (receptors)?
- alpha and beta adrenoceptors (GPCRs)
- SNS postganglionic synapse
Atropine
- muscarinic antagonist
Curare
- nicotinic antagonist
What is the effect of blocking muscarinic receptors on ACh?
ACh can act on ganglionic synapses in ANS or sweat, adrenal glands
e.g. ACh causing vasodilation (usually via NA & A in the SNS)
Alpha-adrenoceptors are located in
blood vessels
Beta-adrenoceptors are located in
blood vessels and heart
Adrenaline
- activates alpha and beta-adrenoceptors
- increases HR and BP
Phenylephrine
- a1 adrenoceptor agonist (smooth muscle of blood vessels)
- increases BP, lesser effect on HR (beta)
- nasal decongestant
Isoprenaline
- beta agonist
- heart - causes +HR
- BV SM vasodilation - causes -BP
How do ligand-gated ion channel receptors function?
- ligand e.g. ACh for nicotinic AChRs binds to receptor
- changes its structure, allows ions into cell
- e.g. Na+ enters cell, causes AP generation and propagation
How do GPCRs function?
e.g. muscarinic AChRs, alpha and beta-adrenoceptors
- 7 transmembrane proteins that bind to G-proteins (Guanine nucleotides)
- activates enzymes yielding a downstream response
What is the structure of the nicotinic ACh receptor?
- 5 subunits
- each has isoforms
- arrange in different subtypes of NicRs found in different tissues (e.g. muscle, ganglionic, CNS)
- has extracellular, transmembrane, and cytoplasmic regions
