Neuromuscular Junction & Synpase Flashcards
The neruomuscular junction connects what type of muscle to what type of nerve
review: UMN v LMN
Muscle: skeletal muscle = striated, multinucleated & under voluntary control
(cardiac and smooth muscle is under autonomic control)
Nerve: Voluntary Control Nerves: aka corticospinal tract with UMN and LMN
- where they decend from the cortex, to the medulla, cross at the level of the pyramids to the contralateral side then contiue on & eventaully synpase in the ventral horn (UMN –> LMN) & then exit and go to the junction
UMN: from cortex to the anterior horn of the SC
- lesion = hyperreflexia & increased tone
LMN: from the anterior horn of SC to the NMJ
- lesions: hypotonia & decreased reflex
- LMN: can be alpha neurons or gamma neurons
Explain the muscle fiber morphology
from large to small…
- muscle
- made up of multiple fasicles
- fasicles are made of multiple muscle fibers
- muscle fiber = one muscle cell
- inside a muscle fiber (surrounded by a sarcolemma of sarcoplasm)
- myofibrils make up the muscle fiber; surrounded by T tubules & sarcoplasmic reticulum
- each myofibril is made of multiple sarcomeres: the single contractile unit of a muscle: with actin and myosin filaments for contraction
every muscle fiber (Cell) contains only 1 end plate
what is the different between an alpha motor neuron and a gamma motor neuron
ALPHA NEURONS
- the lower motor neuron you think about; a TRUE motor neuron
- moderate diameter, myleinated nerve with very fast speed of signalling
- these alpha motor neurons innervate true skeletal muscles (aka extrafusal fibers) those which are type1 slow or type 2 fast twitch fibers
GAMMA NEURONS
- are thin neurons which are mylinated, but slower to transmit thesignal l(because they are thin)
- these beta neurons are responsible for innervating the intrafusal fibers: located inside the muscle spindle
- the goal of the intrafusal fibers is to callibrate the muscle spindle size
what is a muscle spindle, how does it relate to gamma neruons
Bag v Chain fibers (axons)
a muscle spindle = the area within a muscle which is responsible for proprioception signaling
- responsible for sensing length and rate of length changes within the muscle fiber
- the interfusal muscle fiber found within the spindle sends messages about proprioception back to the CNS by way of the gamma motor neuron
- the signal travels to the SC on Type 1A BAG fibers & Type II CHAIN fibers
Bag v Chain Fibers
- types of intrafusal fibers: striated and multinucleiated fibers
- Bag Fibers = have Type1A axons =for RATE OF length changes
- Chain Fibers = have Type II axons = for length
what is the Golgi Tendon Organs
what is thier role
Golgi Tendon Organs
- a braided strand of collagen in the tendon of a skeletal muscle, at the junction of the tendon/muscle connection
Role
- signal to the spainl cord through Type 1B fibers to tell about force/muscle tension
-“holding a raw egg v a hard boiled one”
Motor Fiber Types
Type 1: Slow Twich Fibers: slow oxidativefibers so they use oxygen and glucose to make energy = endurance muscles (back muscle to stand upright)
Type IIa = Fast Twitch Fibers: fast oxidative fibers so they use oxygen and glucose BUT can switch to anaerobic (non-oxygen dependent) if needed; fatigue quicker than type I
Type IIb = Fast Glycolic Fibers: use anaerobic glycolysis used for power
- a mix of type I and II in muscles depedning on function & amoutn of each type can change depednding on activity levlel
what is a minature end plate potential
how does it happen
MEPPs: a small firing of the potential when the neuron is as rest to the muscle: but its not enough of a signal to trigger an AP to occur & produce a result
HOW
- Ach leaks from the LMN axon terminal regularly without the ability to stimulate an AP
- the Ach floats acorss and binds to a nicotinic receptor (0.4 mV of depolarization)
- need approx. 100 mV of energy to fire an AP
how does an AP trigger the contraction of a muscle fiber
- an AP reaches the axon termianl of the alpha motor neruon
- voltage gated Ca+ channels open: the calcium pours into the cell & this triggers Ach to be released from the vesicles its stored in
- the Ach floats across the cleft, binds to the nicotininc receptors on the motor end plate of the fiber
- when FINALLY enough Ach binds, this triggers an end plate potentail to occur
- the resting potential of the motor endplate is -70 –> -100 mV
- the ach binding depolarizes the muscle fiber until the threshold is met: -50 mV is the threshold
- this triggers a true AP to occur & Na+ floods, transfers signal down the plate
- the EPP flows down the T-tubule surroudning each muscle myofibrils
- the signal on the T-tubules reaches the muscle storage of Ca+ in the sarcoplasmic reticulum
- the Ca+ is released, binds to troponin (on actin) and allows myosin to bind to actin
- the bridge is formed and ATP is released, and the filamets side = contraction
- once ATP binds to myosin, it breaks the bridge between actin and myosin
- K+ channels open & repolarization occurs
- residual Ach is broken down by acetylcholenesterase
- choline is recycled and the acetate diffuses
how is Ach made
types of Ach receptors
Choline + acetyey Co-A = Ach
- the ingerdients are shuttled to the axon termianal to make Ach at the terminal via an Na-dependent choline transporter
- then Ach transported to vesicles via VAT: vesicle associated transporter
Ach Receptors
- Nicotinic and Muscarnic receptors = Ach receptors
Nicotinic Receptor
- a ligand-gated ion channel: allowing the passage of Na+ and other cation when Ach binds
- made of 5 subunits
- when Ach binds: opens channle & allows cations through
Where are Nicotinic receptors
what are agonists for this receptor
antagonists?
Nicotinic Receptors: Ach receptors
- NJM: neuromusc. junction
- presynpatic parasympathetic synpase
- adrenal medulla
- within the CNS
Pharmacology of the Receptor
agonists: nicotine and Ach
antagonists: venons and toxins (bungarotxin & tubicurarine)
botox is technically not an antagonists of the receptor, it just prevents the inital release of Ach at the pre-synaptic nerve termial from being able to dock inside a vesicle
what are the three states of a nicotinic receptor
- active/open state: the NT is bound & Na+ channel is functioning
- desensitized: NT bound & Na+channels NOT functioning
- Resting: NT is NOT bound & Na+ channels NOT functionig
with repeated stimulation: the Ach receptors can be desensitized (they get overwhelmed!!!) - this results in a decrease muscle fiber contration force
Motor Unit & Motor Points
Motor Unit = all the indivudal muscle fibers which are innervated by a singal alpha motor neuron ( 1 AMN to multiple muscle fibers (cells) so they function as a contractile unit!)
- in areas where there are finer movements, there are less muslce fibers per AMN (ex. like in the eyes)
Motor Points = where the motor nerves enter the muscle belly on a muscle in the body, important for eletrical stimulation tests & anesthesia
- can have multiple motor points for 1 muscle
Muscle Twitch v. Motor Unit Firing v Muscle contraction
one motor neuron will simultaneously fire EPPs to all the muscle fibers it contains within its motor unit
- the EPPs of the fibers within the unit = TWITCH
- a twitch can be measured by a myogram
- the more force of contraction needed: the more motor units are recreuited
- when the units are stimulated more frequently: this increased force as well
- sustained stimulation/effort will fire multiple muscle fibers
- this effort comes from the motor cortex (the number of firings will be decided here)
Nerve Conduction Study
EMG
Nerve Conduction Study
- peripheral nerve study
- 2 electrodes placed prox. and distally = measure conduction velocity * other things
helpful for = PN disorders like demyleinating ones & helps differential between PN v CN lesion
EMG
- electromyleogram
- needle or surface sensor to detect the activity of the muscle to test contraction at max and minimum
- single fiber EMG can detect the contraction og a single muscle fiber AP
Myasthenia Gravis
- a progressive autoimmune disorder within unknonw etiology
- the antibodies attack the Ach nicotninc receptor at the NMJ
- symptoms when 30% of the receptors are destoryed
- effects extraocculra muslces a lot (not pupillary or constrictors) = because more fast twitch Type II fibers here so they fatigue quick and need teh Ach fast
- ptsos is first sign
- bulbar weakness: the lower CN so dysphonia, dysphagia etc.
- proximal leg weakness in hips
Flares
- stress, heart, surgery & overexerstion
MG crisis: the flare of all symptoms + respiratory distress due to respitory muscles inpacted
Clinical Dx. with antibody tests
Treatment
treat with acetylecholinesterase inhibitors (prolong Ach timein the synpase) mestinon
+ steroids (prednisone) to sup. immune system
+ thymectomy if needed (because of Tcell and antibody role
