somatic nervous system

what is the somatic motor system responsible for

reflex arc which involves the use of interneurons to perform reflexive actions

voluntary control of the body movements via the use of skeletal muscles

where are cell bodies

in the brain stem

how is information passed in the somatic motor innervation

in the form of electrical impulses which is relayed to and from the CNs to the neuromuscular junction which converts electrical signals into chemical signals allowing for muscle contraction

what is the motor unit

motor neuron and muscle fibre it innervates. a single axon innervates many fibres

what is the neuromuscular junction

a synaptic connection between the terminal end of a motor nerve and a muscle. action potential transmits from nerve to the muscle

where is the site for the action of drugs and diseases

neuromuscular junction

main parts of neuromuscular junction

presynaptic (nerve terminal), postsynaptic (motor endplate) and area between the nerve terminal and endplate (synaptic cleft)

how is ACh released at the neuromuscular junction

action potential causes depolarisation and an influx of calcium at nerve terminal. ACh released from storage vesicles into the synapse

what is ACh metabolised by

acetylcholine esterases

what is nicotinic receptors

ligand-gated ion channel

nicotinic receptor subunits

alpha, beta, delta, gamma

how many sites on the nicotinic receptor does ACh bind to

2 sites

the cation channel in nicotinic receptors

cation channel opens for 1 msec. sodium in and potassium out. depolarization of end plate

slide 9

what happens when ACh binds to nicotinic receptors

sodium influx and end plate potential generated which initiates opening of proximal voltage-gated sodium channels- amplification of ion flux and action potential in muscle cell

when does ACH have no affect

when applied to the muscle away from the end plate. signal rapidly terminated by ACh esterase

ways that drugs can interfere with cholinergic transmission at neuromuscular junction

block nicotinic receptors, decrease ACh at NMJ or increase

slide 13

what is 1 drug list NMJ

binds to nicotinic receptor at NMJ as a competitive antagonist.

how does 1 drug on NMJ work

much more ACh is released when NMJ activated so need to block about 90% OF RECEPTORS TO HAVE ANY EFFECT. blocking receptors causes a decrease in end-plate potential so no action potential is generated

synthetic derivatives from 1 NMJ

atracurium, 2 and 3 NMJ

slide 18

what is alpha-bungarotoxin

inhibits ACh binding (post-synaptic) so inhibits ACh-induced electrical response. irreversible binding to the nACh receptors at NMJ

Side effects of non-depolarising blockers

hypotension-due to ganglion blockade

histamine release from mast cells- bronchospasm in sensitive individuals and not related to nicotinic receptor

respiratory failure- assisted ventilation used

autonomic ganglion block at high doses

M2 blockade (gallamine, pancuronium)- tachycardia

the difference between non-depaloraising agents and depolarising blocking agents in NMJ blocking drugs

non- NACh receptor antagonists

depolarising- weak nicotinic agonists

slide 22 onwards

the chemical equations of ACh biosynthesis

Acetate + coenzyme A → acetyl-CoA (AcCoA synthetase)

acetyl-CoA + choline → acetylcholine (choline acetyltransferase)

Ach → choline + acetate (acetylcholinesterase)

the types of acetylcholinesterase

a neuronal one which play a role in the homeostasis of ACh in the synaptic cleft and the other a plasmatic one

the rate limiting step in the synthesis of ACh

reuptake of choline

5 drug list ACh

a competitive inhibitor of choline uptake, acting presynaptically, blocks reuptake of choline by the high-affinity choline transporter affect somatic and autonomic nervous system

7 drug list ach

reduce ach release affect somatic and autonomic nervous system

triethylcholine

its transported. acetylated, ATC stored and release- false transmitter- no depolarising actions. affect somatic and autonomic nervous system

ach release

action potential conducted along motor nerve via Na+ influx. membrane depolarisation and influx of calcium at nerve terminal through voltage-gated ca2+. ach released from storage vesicles into the synapse

6 drug list NMJ

without Na+ channels no depolarisation no calcium channels open. heat-stable, respiratory failure, muscular paralysis

slide 16 and 17

6 drug list ach

produced by clostridium botulinum. spores multiply in preserved food (anaerobic) and cause botulism- food poisoning. home canned food low in acid. irreversible, progressive parasympathetic, motor paralysis, dry mouth, blurred vision, difficulty in swallowing, respiratory paralysis. transported into nerve terminals, cleaves SNARE proteins required for vesicle fusion and release. blocks for months

6 drug list ach A vs B

A- SNAP (botox)

B- VAMP (myoblock)

6 drug list ach uses

migraine, excessive sweating, cerebral palsy, strabismus, cervical dystonia, eyelid spasm

5 drug list NMJ

inhibits ach binding post synaptically and hence skeletal muscle response

5 drug list NMJ beta version

paralysis, respiratory failure and death, acts on presynaptic motor nerve terminals to block release of ach

where is acetylcholinesterases found

in the synaptic cleft at cholinergic synapses and profound autonomic activation- parasympathetic SLUDGE and activation of chromaffin cells in adrenal glands

regions of AChE

recognition- anionic site that binds the choline moiety of ACh

catalytic site breaks down ACh to acetate and choline

acetylserine is rapidly hydrolysed to return AChE to active conformation

9 drug list ach

short acting. ionic bond with ache at anionic site. diagnostic use in myasthenia gravis. competitive

8 drug list ach

competitive site at anionic and esteric sites. form carbamyl as opposed to acetyl esters at the esteric site. carbamylate enzyme complex much slower to hydrolyse. recovery of anaesthesia

10 and 11 drug list ach

chemical weapon, irreversible, absorbed through lungs and skin

slide 31 onwards