Neurotransmitters; NMJ to myocyte Flashcards
The two most common neurotransmitters released by the neurons of the ANS are
- Acetylcholine
2. Noradrenaline
What are the two types of acetylcholine receptors?
Muscarinic and Nicotinic
Muscarinic receptors are of what type (of the four different classes of intracellular receptors?)
GPCR/ metabotropic
What are the 5 subtypes of muscarinic receptors?
M1 - M5
M1 - Neural M2- Cardiac M3 - Glands/smooth muscle M4 - CNS M5- CNS
Muscarinic receptors are located post-synaptically in _________ muscle, __________ muscle, and ________.
smooth, cardiac, glands
Nicotinic receptors are what type of receptors? (Of the four types)
Ionotropic
What is the main ion that passes through nicotinic receptors?
Mainly sodium channels, but some potassium can also go through
This neurotransmitter contracts smooth muscle, dilates blood vessels, increases bodily secretions, and slows heart rate
Acetylcholine
What is the chief neurotransmitter of the parasympathetic nervous system?
Acetylcholine
Describe the action of acetylcholine
- Contracts smooth muscle
- Dilates blood vessels
- Increases bodily secretions
- Slows heart rate
Norepinephrine acts on what type of receptors?
Adrenoreceptors (metabotropic/GPCR)
What tissues contain alpha-adrenoreceptors?
Blood vessels of organs and tissues (except skeletal muscle)
Which substances act on alpha adrenoreceptors? (Two hormones and one drug)
- Noradrenaline
- Adrenaline
- Isoprenaline
What is an antagonist that blocks the activity of alpha-adrenoreceptors?
Phentolamine
In what tissue would you find beta1 adrenoreceptors?
Cardiac
In what tissue would you find beta2 adrenoreceptors?
LUNGS, uterus, muscle, and coronary vessels
In what tissue would you find beta3 adrenoreceptors?
Adipose tissue
Which substances act on beta adrenoreceptors? (hint: same 3 as alpha adrenergic receptors)
- Noradrenaline
- Adrenaline
- Isoprenaline
Which type of receptor is sensitive to upregulation and downregulation? (Think of beta blockers)
Beta adrenergic receptors
What is an antagonist that blocks beta-adrenergic receptos? (Beta1?)
Propranolol
Which neurotransmitters are catecholamines?
Noradrenaline and adrenaline
AKA Norepinephrine and epinephrine
Beta receptors are associated with what type of beta subunit on the GPCR?
G alpha S
Beta receptors associated with G alpha subunit activate which enzyme?
Adenylate cyclase
Adenylate cyclase activates which second messenger?
cAMP
alpha 1 receptors are assiated with which G alpha subunit?
G alpha q
G alpha q is associated with which enzyme?
Phospholipase C (activates)
Activating phospholipase C is associated with which second messengers?
IP3 and DAG
What ion is associated with increasing PLC, IP3, and DAG?
Calcium
alpha 2 receptors are associated with which G alpha subunit?
G alpha i (i for inhibit)
Beta receptors (1,2 and 3) are associated with which G alpha subunit?
G alpha s (s for stimulate)
The action of this neurotransmitter is vasoconstriction of blood vessels, increase BP, increase contraction of the heart, increases blood glucose and increasescirculating free fatty acids.
Norepinephrine
What is the most important neurotransmitter of the sympathetic nervous system?
Norepinephrine
This neurotransmitter is secreted by the chromaffin cells of the adrenal medulla.
Adrenaline/epinephrine
What is the role of adrenaline?
To produce a sympathetic response
What receptors does adrenaline act on?
Same as norepinephrine: alpha 1, alpha 2, beta 1/2/3 receptors
Drugs can mimic or block the actions of NT’s at their receptors. Name four types of receptors found within the nervous system (think of the four main neurotransmitters)
- Cholinergic
- Adrenergic
- Serotonergic
- Dopaminergic
What is the main degredation method for adrenergic neurotransmitters?
Re-uptake
Though NT can also be metabolised by enzymes such as MAO and COMT
Neurotransmitters can be metabolised by which enzymes? (Two examples mentioned in lecture)
MAO
COMT (catechol-o-methyltransferase)
Sympathomimetic drugs ___________ the sympathetic nervous system
stimulate
What type of drugs (a general term) inhibit the action of the sympathetic nervous system?
Sympatholytic
In what condition could you use a muscarinic antagonist? (Think lungs, opposing parasympathetic response)
Asthma (results in bronchdilation)
What type of drug is used in cases of severe hypotension, such as in shock? (Drug that acts on which receptors?)
alpha 1 adrenergic AGONISTS are systemic vasoconstrictors used in the treatment of shock
What condition would an alpha 1 antagonist be used to treat?
Hypertension, as an alpha 1 ANTAGONIST would lower blood pressure
Name the drugs that act as adrenergic agonists
- Adrenaline
2. Isoprenaline
Name the drug that is an alpha 1 adrenergic ANTAGONIST
Phentolamine
What is the drug that is a Beta 2 adrenergic agonist?
Salbutamol (asthma)
Name a beta adrenergic ANTAGONIST
Propranolol
Specialised intercellular connections between a neuron and a muscle are called…
(don’t overthink it!)
Neuromuscular junctions
Which neurotransmitter acts at the skeletal-NT junctions?
Acetylcholine
Acetylcholine is synthesized in the ___________ and packaged into synaptic __________.
cytosol, vesicles
What initiates the action potential in the muscle cell? (hint: binding of a NT)
The binding of ACh to receptors in the motor end plate
What is the membrane of the myocyte called?
The sarcolemma
What structure expands the surface area of the myocyte, allowing action potentials to propogate into and towards the centre of the cell?
T-tubules
Vesicles bud off the __________ and are loaded with ACh
endosome
The key role of the endosome in the neuromuscular junction is the ____________ of vesicles.
recycling
Fusion of the vesicles with the membrane is __________ dependent.
Calcium
A sarcomere is the region from one _______ to the next ________.
Z line, Z line
A large structural protein within sarcomeres
Titan
What happens after T tubules depolarise (during excitation-contraction coupling)?
calcium channels of the sarcoplasmic reticulum open
During excitation-contraction coupling, what happens after calcium levels increase in the sarcoplasmic reticulum? (Interaction of two proteins; two words)
Myosin interacts with actin - crossbridge cycling
Once the myosin-binding sites are exposed, and if sufficient ____ is present, myosin binds to actin to begin cross-bridge cycling.
ATP
After the sarcomere contracts________ is returned to the sarcoplasmic reticulum via ________ pumps.
Calcium, calcium
Influx of which ion results in the physical change in the organisation of the thin filaments (actin) in cross-bridge cycling? (Due to voltage change in sarcoplasmic reticulum)
Calcium
Which ion is KEY in excitation contraction coupling? (Depolarises membrane?)
Calcium
What chemical change in ATP results in a change to the head group angle in the crossbridge cycle?
Hydrolysis of ATP –> ADP
This is the stage of the crossbridge cycle where the release of a phosphate changes the head-group angle, causing the thin filament to move relative to the thick filament.
the power stroke
A single contraction of a muscle fibre
twitch
This is where a myocyte continuously generates its maximal force for a prolonged period (2x twitch duration)
Tetany
Breathing ceases after death, which means cells rapidly deplete levels of _______
ATP
The lack of ________ after death means ________ cannot be pumped back into the sarcoplasmic reticulum
ATP, calcium
Crossbridge cycling contraction continues to occur after death because _______ remains high in the sarcoplasm
calcium
Rigor mortis: The crossbridge cycle stops just after the ________ _______ with myosin still bound to actine (with the muscle contracted).
power stroke
When does rigor mortis end?
When the muscle tissue degrades
Succinylcholine is what type of drug?
ACh agonist. Used to treat muscle weakness in conditions like MG.
Curare blocks what type of receptors?
Nicotinic Acetylcholine receptors
Neostigmine and physostigmine are what type of drugs (hint: enzyme inhibitors)
Acetylcholinersterase inhibitors. Prevent degredation of ACh. Treats Alzheimers, MG, urinary retention
What condition could curare potentially be used to treat?
Tetany, as it causes flaccid paralysis