bruno (L4-8) Flashcards
(54 cards)
organisation of the peripheral nervous system (pns)
- somatic ns (skeletal muscle)
- autonomic ns // sympathetic ns and parasympathetic ns (targets all except skeletal muscles)
- enteric ns (guts)
types of nerve fibres (2)
AFFERENT fibres carry sensory information to the CNS
and
EFFERENT fibres carry signals from the CNS to the periphery
3 types of horns
dorsal horn (sensory inputs, on the back of the spinal cord)
lateral horn (spinal preganglionic neurones of ANS)
ventral horn (somatic motor neurons)
the 5 steps to communication in the CNS/PNS to synaptiic transmission
- Synthesis of neurotransmitter
- Store neurotrans in vesicles - 2 reasons to store (protect neurotrans from enzymes that can metabolise them, package neurotrans at high conc in vesicles so that when released, the conc is much higher than in the synaptic cleft and achieve a burst)
- Release neurotrans - many steps are involved, you have to dock the vesicle with the ??? calcium catalyses the fusion of vesicles and the axon membrane, exocytosis, retrieve the membrane to recycle by endocytosis
- Activation of neurotrans receptors - 2 types (ligand gating receptors with ion channel through them, G protein coupled receptors). Neurotran activates either G protein one only, or both.
- Inactivation - remove neurotrans by 2 mechanisms (enzyme present that metabolises the neuro into inactive components, or remove complete neurotrans or breakdown product of the neurotrans). This is to achieve a phasic fashion for the neurotrans to have a high conc gradient and ensure a high impact.
efferent pathway of somatic nervous system
it consists of a single neurone
cell body of neuron lies in the ventral horn of the spinal cord or nuclei within higher brain centres
motor neuron (efferent) runs directly to the skeletal muscle fibres synapses at a specialised structure (NMJ neuromuscular junction, or endplate)
efferent pathway of somatic nervous system
consists on 2 neurons
- preganglionic neurone
- ganglion
- postganglionic neuron
classification of somatic and autonomic synapses
- somatic motoneurones
1 neuron from cns to skeletal muscle
nAChR - parasympathetic motor neurones
2 neurons from cns to ganglia to eg salivary glands
nAChR pregang / mAChR postgang - sympathetic motor neurons
2 neurons from cns to ganglia to blood vessels
nAChR pre / NA post
OR: 2 neurons from cns to adrenal medulla to all cells
nAChR pre / adrenaline post
OR: 2 neurons from cns to ganglia to sweat glands
nAChR pre / mAChR post
classification of parasympathetic nervous system
LONG PREGANGLIONIC NEURON / SHORT POSTGANGLIONIC NEURON
from brain stem (medulla) to different tissues
-2 neurons (medulla to peripheral ganglion to pupils or salivatory glands)
-2 neurons with vagus (X) nerve as a preganglionic nerve
(medulla to peripheral ganglion to bronchi, heart, gallbladder, gut motility, bladder, genitals)
classification of
sympathetic nervous system
SHORT PREGANGLIONIC NEURON / LONG POSTGANGLIONIC NEURON
from spinal cord to ganglion in sympathetic chain to different tissues
- 2 neurons through sympathetic chain (blood vessels, hari erection, sweat glands)
- 2 neurons through sympathetic chain (pupils, bronchi, heart rate and contractility)
- 2 neurons, ganglia after the sympathetic chain (gut motility, liver, renal)
- 1 neuron to adrenal glands
- 2 neurons through hypogastric ganglion (vas deferens in ejaculation)
Probability of the neurotransmitter releasing
Probability of the neurotransmitter releasing across the synapses is rarely 1, which means that if you send an action potential down a nerve the chances that one of the viral posities will release neurotransmitter is not one so it will not happen every single time
the probability is actually quite low at these varicosities, which is why we have so many vesicles. the probability of releasing something that can be modified can be increased buy the circuits of the brain to ensure that the response will be put into action.
acetylcholine in the parasympathetic NS
ACETYLCHOLINE is the neurotransmitter released from all parasympathetic postganglionic neurones at the neuroeffector junction
how do you classify synapses
Synapses can be classified according to the transmitter released from the presynaptic neurone.
At synapses where the presynaptic neurone synthesises and releases acetylcholine (ACh) transmission is classed as cholinergic. Receptors upon which ACh acts are called cholinoceptors.
Two classes of cholinoceptor in the NS
- nAChR
Nicotinic cholinoceptors
are activated by ACh or the tobacco alkaloid nicotine but not by muscarine.
ALL ARE LIGAND GATED ION CHANNELS - mAChR
Muscarinic cholinoceptors
are activated by ACh or the fungal alkaloid muscarine but not by nicotine.
ALL ARE G PROTEIN COUPLED RECEPTORS
define noradrenergics and name 2 types of their receptors
At synapses where the transmitter is noradrenaline, transmission is described as noradrenergic and the receptors activated are called adrenoceptors.
Two classes of adrenoceptor are found
in the nervous system:
α-adrenoceptors and β-adrenoceptors
molecular structure of nicotinic cholinoceptors (subunits, domains etc)
consists of 5 subunits (αβγαδ) to form a pentameric ligand gated ion channel
Extracellular domain will respond to ach
Transmembrane domains - M2 domain creates the ion channel, M2 determines ion conduction or ion cell activity of the channel.
how do ions flow through the nicotinic cholinoceptors?
the Ach has to bind to the 2 a subunits for the ion channel to open by shape change, ions move down their electrochemical gradient
OR IONS (EG SODIUM)
Sodium ions are repelled from the positive ion dense region at the bottom. Fenestrations are found on the sides of the structure of the channel. They could be roots for ions to flow through.
so the ions flow through the channel from the top and out its sides
g couple protein coupled receptor cycle
by agonist binding, the receptor then becomes occupied and causes a conformational change which allows it to interact with the alpha subunit of the G protein
alpha subunit then loses its affinity to the GDP and its affinity to GTP increases.
Activated the G protein, it goes to interact with its target proteins (activate or inhibit)
To stop the cycle - alpha subunit metabolises the GTP to GDP. GTPase activity switches off the signal. Returns to resting state.
difference in rates of activation between nicotinic receptors and ligand gated channel
Process occurs over a few milliseconds while the activation of a ligand ion gated channel occurs in many seconds so the time scale is very different
this is because nicotinic receptors are found at the skeletal muscles where we need very quick control of activity, whereas in the gut we don’t need quick control so we can use ligand gated channels
Signalling of these 2 processes is very different
process of Botulinum toxin affecting the neuromuscular junction
The fusion of the vesicles to the presynaptic membrane gets interactions of many proteins (snare, syntaxin etc)
They tether the synaptic vesicle to the presynaptic membrane
Ca enters cell, tethers are taken up, take it to close proximity to the membrane, fusion, release of neurotransmitter
B toxin can interfere with one of the proteins (synaptotagmin) to get a complex form
Internalised through endocytosis - bond between HC and LC is broken.
LC cleaves the SNARE proteins
→ PARALYSIS
define mEPP and the result of its summation
Release of a vesicle gives a “quanta” of transmitter
At NMJ each quanta gives rise to a miniature end plate potential (mEPP) via activation of nAChRs
mEPPs summate to give an end plate potential (EPP), which, if large enough, can initiate an action potential (AP) and hence muscular contraction
2 phases of NMJ block
PHASE 1 BLOCK -
persistent activation of endplate nicotinic receptors by suxamethonium
Causing strong depolarization of the muscle which results in inactivation of voltage gated sodium channels (these channels need to rest but as you depolarise the membrane then it tends to deactivate the voltage gated sodium channels). so they become desensitised
PHASE 2 BLOCK - Because nicotinic receptor has been heavily stimulated, so leads to desensitisation of receptors, maintains the blockade of NMJ
ganglionic blockers
ganglion blockers
reduce the actions of both the sympathetic and parasympathetic nervous systems
Both sympathetic and parasympathetic NS have ganglion so blocking ganglia will block the whole autonomic nervous system
difference between the autonomic ganglia and NMJ ganglia
These nicotinic receptors are diff from the ones at the NMJ
Before, they knew this because the drugs used at NMJ don’t work at ganglion. (this is weird because they both respond to nicotine but only one of them response to suxamethonium)
Subunit composition for nicotinic receptors at the ganglia is different
Pharmacology of receptors is diff they have their own antagonists and agonists
muscarinic receptor subtypes
M1 neutral (Autonomic ganglia) - Modulation of ganglionic transmission
M2 cardiac (Cardiac atria and conducting tissue) - Cardiac slowing
↓ force of contraction
M3 glandular (Salivary glands and smooth muscle of gut) - Secretion of saliva and ↑ gut motility
M4 (CNS) - Modulation of synaptic transmission
M5 (CNS, substantia nigra) - Modulation of synaptic transmission
