4. NMJ Flashcards
Motorneuron discharge - spread depol along what
What does this lead to - by what receptor
What does this then bind to
cross link - between what
passive or active process
Discharge of motoneurones results in the inward spread of depolarisation along T-tubules.
Depolarisation of the T-tubule activates the sarcoplasmic reticulum via dihydropyridine receptors, which are voltage-gated Ca2+ channels in the T-tubule membrane.
Ca2+ diffuses to thick and thin filaments and binds to troponin C, which displaces tropomyosin and uncovers myosin-binding sites on actin.
Hydrolysis of ATP results in cross-linkages between actin and myosin and sliding of thick on thin filaments, producing shortening. This is an active process as Ca2+ is pumped back into the sarcoplasmic reticulum.
At rest, the myosin head is complexed with ADP and inorganic phosphate
Thin filaments made up of
Thick filaments - made up off
What does calcium bind to - what does that change
How many calcium binding sites on troponin
The thin filaments are made up of actin, tropomyosin, and troponin.
The thick filaments, which are about twice the diameter of the thin filaments, are made up of myosin.
Troponin, actin, and tropomyosin all constitute thin filaments. However, during the initiation of muscle contraction, Ca2+ binds to troponin C and tropomyosin is displaced laterally, which exposes the binding site for myosin on actin.
Troponin C contains 4 Ca2+ binding sites for the Ca2+ that initiates contraction.
Ache - made / secreted where
where does it reside
what does choline acetlytransferase synthesise
what type of receptor resides in the NMJ
How soon does it hydrolyse
Acetylcholinesterase (AChE) is made in and secreted by muscle cells and it lies mainly in the junctional clefts, but remains attached to the muscle by thin stalks of collagen.
Choline acetyltransferase catalyses the synthesis of acetylcholine (not AChE).
Once released into the synaptic cleft, most of the acetylcholine reaches the postjunctional receptors, which at the neuromuscular junction are nicotinic not muscarinic receptors.
Once released from the nicotinic receptors acetylcholine is hydrolysed by AChE, which occurs within 1 millisecond of its release.
Name parts of myofibril
band
discs
zones lines
Naming convention of the regions of the myofibril is based on their microscopic appearance.
Myofibrils are subdivided into sarcomeres by Z discs.
Each sarcomere is comprised of A and I bands. The I band contains only actin. The A band comprises mostly myosin but there is some actin overlap. The part of the A band that contains myosin without overlapping actin is known as the H zone and central to this is the M line.
what helps determine aerobic capacity
What has the highest percent mitochodnira
The mitochondrial density and blood supply of a muscle cell is a chief determinant of aerobic capacity.
Mitochondria represent 30-40% of the ventricular mass. This high metabolic rate creates serious diffusion problems within cardiac muscle. There is a high capillary density and the cells are small, with a high surface to volume ratio.
In skeletal muscle of normal individuals mitochondria represent 2-3% of muscle mass. Electron microscopy studies have shown both the number and size of the mitochondria increase with endurance training.
Human skeletal muscle is composed of a heterogeneous collection of muscle fibre types. These muscle fibre types can differ histologically, biochemically, and physiologically.
The biochemical classification is based on muscle fibre myosin ATPase histochemistry:
Type 1 (slow twitch): These muscle fibres usually depend upon aerobic glycolytic metabolism and aerobic oxidative metabolism. They fibres are rich in mitochondria and myoglobin, have a good blood supply, and are resistant to fatigue. The power of twitch is less than that of type II fibres. These slow twitch muscle fibres are useful to help athletes in endurance events, such as marathon running. Type II (fast twitch): These muscle fibres are sub-divided, with type IIa also relying on aerobic/oxidative metabolism but type IIb relying on anaerobic/glycolytic metabolism. These fast twitch muscle fibres are therefore useful to help athletes for short bursts of activity (i.e sprinting). Fast twitch muscle fibres are more easily fatigued but produce short bursts of intense power. The mitochondrial density is highest in type I skeletal muscle.
Type IIa fibres are also sometimes known as fast oxidative fibres and are a hybrid of type I and II fibres. These fibres contain a large number of mitochondria and myoglobin, hence their red colour. Resistance training can turn type IIb fibres into type IIa fibres, due to an increase in the ability to utilise the oxidative cycle.
Type IIb known fibres (fast glycolytic) are white in colour due to a low level of myoglobin and also contain few mitochondria. They produce ATP at a slow rate by anaerobic metabolism and break it down very quickly. This results in short, fast bursts of power and rapid fatigue. They are particularly found in muscles and legs.
Type I > type IIa > type IIb.
Botox
is what
ow does it work
Botulinum toxin (BT) is a potent neurotoxin produced by the bacterium Clostridium botulinum. There are seven sero-subtypes (A, B, C, D, E, F and G) all of which bind to extracellular glycoproteins on cholinergic nerve terminals and block presynaptic acetylcholine release.
BT also has an affect on the spinal stretch reflex of muscle fibres by blocking intrafusal muscle units with a reduction of Ia/II afferent signals reducing muscle tone without affecting muscle strength (reflex inhibition).
BT also blocks efferent autonomic fibres to smooth muscles and to exocrine glands.
What muscle fibre has the fastest twitch response
How are muscle subdived
what are the types
what is the metabolism here
What are the twitch responses like in cardiac & SM compared to skeletal
Type IIb skeletal muscle has the quickest twitch response of all muscles. They are able to generate short bursts of intense power.
The biochemical classification is based on muscle fibre myosin ATPase histochemistry into two groups:
Type 1 (slow twitch): These muscle fibres usually depend upon aerobic glycolytic metabolism and aerobic oxidative metabolism. These muscle fibres are rich in mitochondria, have a good blood supply, rich in myoglobin and are resistant to fatigue.
Type II (fast twitch): These muscle fibres are sub-divided into type IIa also relying on aerobic/oxidative metabolism but type IIb fibres rely on anaerobic/glycolytic metabolism. Fast twitch muscle fibres are more easily fatigued but produce short bursts of power.
The twitch speeds of cardiac and smooth muscle are relatively slow compared with skeletal mu
Polysynaptic reflexes
ex
monosynpatic
what
where
Polysynaptic reflexes include the
Protective Vegetative Nutritional and Locomotion reflexes for example, the cremasteric, corneal, inverse stretch and withdrawal reflex.
Monosynaptic reflexes are very fast, originating and terminating in the same muscle, for example, the patellar reflex.
What causes knee jerk reflex
- locatio wise
how many synapes
afferent via what type fibres
what is westphals sign
how does transection cord affect
The knee jerk reflex is secondary to stretching of muscle spindles in the quadriceps muscle, caused by a tap on the patellar tendon and has a single synapse. The afferent pathway is primarily via Ia fibres (dynamic) or A-alpha and secondarily type II sensory fibres (static).
Westphal’s sign is the absence or decrease of this reflex.
Transection of the cord is followed by a variable degree of spinal shock where all reflexes are depressed or absent. Recovery of reflexes may take up to six weeks.
What are the different fibres and what do they do
Class A-alpha fibres provide motor function and proprioception sensation.
Class A-beta fibres carry touch and pressure sensation.
Class A-gamma fibres provide motor function to muscle spindles.
Class A-delta fibres carry pain, cold and touch sensation.
Myelinated Class B nerves are autonomic preganglionic fibres.
Unmyelinated Class C nerves are autonomic postganglionic fibres which also carry pain and temperature sensation.
Reflex arc
Thermorecptors
what fibres
wwhat type are the afferent
size
conduction speed
where do they enter SC
Efferent pathway what type
size
condction speed
What do C fibres do interms of size speed carry modality
The neural pathway described is a simple primary reflex arc.
Thermoreceptors are specialised receptors in the dermis on the free endings of Aδ and C fibres.
Afferent pathways are the small myelinated Aδ fibres. These fibres are 2-5 µm in diameter and have conduction speeds of between 10 and 30 metres per second. These primary afferents enter the dorsal horn of the spinal cord (the cell body lies in the dorsal root ganglion). In the dorsal horn the primary afferent neurone synapses with an inter-neurone, which in turn synapses with the efferent pathway.
Efferent pathways are the thick myelinated A-alpha fibres. These fibres are 10-20 µm in diameter and have fast conduction speeds of between 60 and 120 metres per second. The effectors are the flexor and extensor muscle groups.
The C fibres are unmyelinated nerve fibres that are 0.5-1 µm in diameter and have the slowest conduction speeds of between 0.5 and 15 metres per second. They carry the modalities of touch, pressure, cold, warm and dull ache.
AP cardiac myocytes ionic changes
decribe pahses in terms of ion changes
The action potential (AP) of ventricular and atrial myocytes, as well as the Purkinje system have the same characteristic ionic changes. The duration is approximately 200 ms and has a resting membrane potential with fast depolarisation and plateau phases.
There are five phases:
Phase 0 (rapid depolarisation) - Increased Na+ and decreased K+ conductances Phase 1 (initial repolarisation) - Ceased Na+ and increased K+ conductances Phase 2 (plateau phase) - Increased Ca2+ conductance Phase 3 (repolarisation phase) - Decreased Ca2+ and increased K+ conductances Phase 4 (resting membrane potential) - Increased K+ and decreased Na+ and decreased Ca2+ conductances.
What is best for monitoring deep NMB - where diaphragmatic conctraction avoided
The post-tetanic twitch count is used to monitor deep neuromuscular blockade for surgery where diaphragmatic contraction is best avoided.
Certain skeletal muscles are relatively resistant to the effects of non-depolarising and depolarising neuromuscular blocking agents.
The most resistant is the diaphragm.
Less resistant are the muscles of the larynx and corrugator supercilii muscles.
The most sensitive muscles are abdominal, orbicularis oris and the peripheral muscles of the limb.
P
Single supramaximal stimulus:
1 Hz to 0.1 Hz (one every second to one every 10 seconds)
The response is proportional to frequency
It does not have much clinical application as it will tell you only if a patient is paralysed or not (no information on degree of paralysis).
Four supramaximal stimulati over 0.5 seconds (2 Hz):
‘Fade’ can be observed and provides basis of evaluation
This pattern of stimulation is used to assess the intensity of blockade (1-2 twitches is appropriate for abdominal surgery)
Reversal agents can be administered if the train of four (TOF) count is 1-2 twitches with medium length acting neuromuscular blocking agents.
