Module 2 Flashcards
Blocks release of Ach from presynaptic terminals
Botulinum toxin (botox)
a drug that blocks the gating action of Ach on the Ach channels by competing for ACh receptor sites on motor end plate
Curare
Inhibits acetylcholinesterase
Neostigmine
Blocks reuptake of choline into presynaptic terminal
Hemicholinium
Antibody directed against the ACh receptor
Myasthenia gravis
What is the effect of AChE inhibitor?
Blocks the degradation of ACh, causing an increase in the endplate potential, and prolongs the action of ACh at the motor endplate
- A neuromuscular disease with classic symptoms of weakness and fatigue of skeletal muscles
- Seen more commonly in females, with peak incidence at 20 to 30 years of age
- Men have a peak of incidence at around 50 to 60 years of age
Myasthenia gravis
Classic symptoms of this disease is muscle weakness that increases with repetitive muscle use (eg, chewing) and partially recovers with rest
Myasthenia gravis
- Most common muscular dystrophy
- 1 in 3500 boys (3-5 yo)
- Severe muscle wasting
- Most patients are wheelchair bound by the age of 12
- Respiratory failure in adulthood (30 to 40 years of age)
Duchenne’s muscular dystrophy
What is gower’s sign for Duchenne’s muscular dystrophy?
Using hands to push on legs to stand
- X-linked recessive
- Defect in the dystrophin gene –> deficiency of the dystrophin protein in skeletal muscle, brain, retina, and smooth muscle
Duchenne’s muscular dystrophy
- A large (427 kDa) protein present in low abundance (0.025%) in skeletal muscle
- Localized on the intracellular surface of the sarcolemma in association with several integral membrane glycoproteins (forming a dystrophin-glycoprotein complex)
Dystrophin
- Tethers Myosin to Z lines (scaffolding)
- Binds Z lines to M line
- largest protein
Titin
- Attaches to plasmalemma
- Stabilizes plasmalemma and prevents contraction-induced rupture
Dystrophin
Binds Actin to Z lines
Actinin and Capz Protein
Binds Z lines to plasma membrane
Desmin
- Occurs when contracting muscles are stretched and lengthened too vigorously
- More pain and stiffness than in not-so-vigorous muscle stretching and lengthening (cycling)
Resultant dull, aching pain develops slowly and reaches peak in 24 to 48 hours
Delayed-onset Muscle Soreness
- Pain associated with reduced range of motion, stiffness, and weakness of the affected muscles
- Pain due to inflammation near myotendinous junctions
- Slow recovery, depends on regeneration of the injured sarcomeres
Delayed-onset Muscle Soreness
- A state of contracture several hours after death
- All the muscles of the body go contraction and become rigid even without action potentials
Rigor Mortis
Rigor Mortis results from loss of all the ATP. Why?
It is required to cause separation of the cross-bridges from the actin filaments during the relaxation process
- Muscles remain in rigor until the proteins deteriorate (15 to 25 h later)
- All these events occur more rapidly at higher temperatures
Rigor Mortis
exert opposite effects but operate reciprocally (complementary) or synergistically to produce coordinated responses
Dual Innervation
Single Innervation that has sympathetic only
- sweat glands
- adrenal glands
- most blood vessels
- pilomotor muscle
Single Innervation that has parasympathetic only
- lacrimal muscle (tear glands)
- ciliary muscle (accommodation for near vision)
2 reasons why adrenal medulla is considered to be part of the ANS
- Nerve supply to AM is anatomically and biochemically identical to autonomic preganglionic nerve fibers
- Adrenomedullary cells are embryologically, anatomically and functionally identical to postganglionic autonomic nerve fibers
2 reasons why adrenal medulla is considered a component of SNS and not PSNS
- Origin of nerve supply of AM is thoracolumbar
- Adrenomedullary cells secrete catecholamines (Epinephrine – 80%; Norepinephrine – 20%, the neurotransmitter of sympathetic nerves)
- mydriasis
- increased ABP
- vasoconstriction
- increased in skeletal muscle strength
- increased ventilation
Responses of the Sympathetic Nervous System
- decreased GIT activity
- elevation of plasma glucose and fatty acid levels
- increase in mental activity
Responses of the Sympathetic Nervous System
- lowers threshold in the reticular formation
- redistribution of blood from skin and splanchnic regions towards skeletal muscle
Responses of the Sympathetic Nervous System
location:
- radial muscle of iris
- blood vessels of skin, skeletal muscle, splanchnic region
- sphincters of GIT and bladder
mechanism of action:
- activate phospholipase C and increase the intracellular concentration of IP3
Alpha 1 Receptors
Antagonist of Alpha 1 receptors
Prazosin
location: - prominent in the heart - salivary glands - adipose tissue - kidneys (promote renin secretion) Mechanism of Action: - involves Gs protein activation of adenylcyclase to increase cAMP concentration
Beta 1 Receptors
sites:
- predominate in smooth muscle of airways
- blood vessels of skeletal muscles
- GIT and bladder walls
Mechanism of Action:
- same as beta 1
- involves Gs protein activation of adenylyl cyclase to increase cAMP concentration
Beta 2 Receptors
Potentiates cholinergic effects
Parasympathomimetic Agents
Parasympathomimetic Agents that interact with muscarinic receptors imitating ACh
Pilocarpine
Parasympathomimetic Agents that interacts with nicotinic receptors mimic ACh
Nicotine
Parasympathomimetic Agents that inactivate or inhibits acetylcholinesterase
Neostigmine
Blocks cholinergic effects
Parasympatholytic Agents
Parasympatholytic Agents that inhibit active uptake of choline from the blood to the axon terminal
Hemicholine
Parasympatholytic Agents that inhibits ACh release from synaptic vesicles
Botulinum Toxin
Parasympatholytic Agents that competes with ACh at muscarinic receptor sites
Atropine, Homatropine, Scopolamine
Potentiates adrenergic effect
Sympathomimetic Agents
Sympathomimetic Agents that interact with alpha-receptors
Methoxamine, Phenylephrine
Sympathomimetic Agents that interacts with beta-receptors
Salbutamol (Β2), Isoproterenol (Β1= Β2)
Sympathomimetic Agents that cause release of NE from its storage vesicles
Ephedrine, Amphetamine
Sympathomimetic Agents that prevents reuptake of NE by the postganglionic fibers
Cocaine
Blocks adrenergic effects
Sympatholytic Agents
Sympatholytic Agents that inhibit diffusion of NE out of the vesicle
Resirpine
Sympatholytic Agents that inhibits or blocks NE release from storage vesicles
Guanethedine
Sympatholytic Agents that blocks effects of NE on adrenoreceptors
Phenoxybenzamine, where is this used? pheochromocytoma
Sympatholytic Agents that competes with NE at beta receptors
Propranolol
Drug that does NOT block effects on alpha receptors. It blocks beta-receptors nonselectively
Propranolol
Function of Muscles
- Movement
- Energy Storage
Types of Muscle
- Skeletal
- Cardiac
- Smooth
- extremities, voluntary, striated multinucleated
a. Intrafusal: Muscle Spindle
b. Extrafusal: For Muscle Contraction
i. White/Fast-Twitch Fiber
ii. Red/Slow-Twitch Fiber
Skeletal Muscle
Contraction speed: Slow, prolonged
Myosin ATPase activity: Slow
Major ATP synthesis pathway: Aerobic/ Oxidative
SR Ca pumping capacity: Moderate (SERCA2)
Rate of fatigue: Slow
Type 1: Slow Oxidative (Red Muscle)
Fiber diameter: small Oxidative Capacity: High Glycolytic capacity: Moderate Activities: Endurance Location: Soleus, anti-gravity muscles of the back
Type 1: Slow Oxidative (Red Muscle)
Contraction speed: Fast Myosin ATPase activity: Fast Major ATP synthesis pathway: Glycolysis SR Ca pumping capacity: High (SERCA1) Rate of fatigue: Fast
Type IIB: Fast Glycolytic (White Muscle)
Fiber diameter: Larger (2x) Oxidative Capacity: Low Glycolytic capacity: High (rapid release) Activities: Quickness, Power Location: EOM
Type IIB: Fast Glycolytic (White Muscle)
- can be found in other animals Contraction speed: Fast/ Intermediate Myosin ATPase activity: Fast Major ATP synthesis pathway: Aerobic/ Oxidative SR Ca pumping capacity: High Rate of fatigue: Intermediate
Type IIA: Fast Oxidative (Red to Pink)
Fiber diameter: Intermediate
Oxidative Capacity: Very High
Glycolytic capacity: High
Activities: Uncommon in humans
Type IIA: Fast Oxidative (Red to Pink)
- found in heart; striated; single nucleus (centrally); involuntary
a. Atrial Muscle Fibers
b. Ventricular Muscle Fibers
c. Conductive Muscle Fibers
Cardiac Muscle
- found in colon, GIT, lungs; involuntary
a. Multi-Unit Smooth Muscle
b. Unitary Smooth Muscle
Smooth Muscle
- One nerve, multiple muscle fibers that may act on their own
- Controlled mainly by nerve signals (Ach, NE)
- (-) Gap junctions
- No True Action Potentials (Electrotonic Conduction)
- (-) Spontaneous contractions
- e.g. Ciliary Eye Muscle, Iris, Piloerector muscle, Vas Deferens
Multi-Unit Smooth Muscle
- One nerve, multiple muscle fibers that are act together as one
- Maybe controlled by nerve (Ach, NE), hormones, stretch, local factors
- (+) Gap junctions
- Slow/Pacemaker waves, Spike Potentials and Plateau Potentials
- May exhibit spontaneous contractions
- e.g. Intestines, Bile Ducts, Ureters, Uterus
Unitary Smooth Muscle (aka Syncitial Smooth Muscle, Visceral Smooth Muscle)
- Rhythmic, Intermittent
E.g. walls of the GI and urogenital tracts
Phasic Smooth Muscle
- Continuously active
E.g. Vascular smooth muscle, respiratory smooth muscles, sphincters
Tonic Smooth Muscle
Composition of Skeletal Muscle
Sarcomeres -> Myofibril -> Muscle Fiber -> Muscle Fascicle -> Skeletal Muscle
Surrounds Muscle Fiber
Endomysium
Surrounds Muscle Fascicle
Perimysium
Surrounds Skeletal Muscle
Epimysium
Plasma membrane surround muscle fiber
Sarcolemma
invaginations of the sarcolemma in close proximity to the terminal cisternae of the Sarcoplasmic Reticulum
Transverse Tubules
- Endoplasmic reticulum surrounding myofibril
- Contains Calcium
Sarcoplasmic Reticulum
- Functional unit of the muscle
- Area between two Z lines
- Exhibited by certain muscle types only
- Has thick filaments and thin filaments
Sarcomere
Myosin
- Two Heavy Chains: MYOSIN TAIL
- Free Ends of Heavy Chains + Light Chains: MYOSIN HEAD
- Tails bundled together: BODY
- Arms and Myosin Heads: CROSS-BRIDGES
- Arm-Body and Arm-Head: HINGES
Thick Filaments
o Actin
o Tropomyosin
o Troponin
Thin Filaments
attaches troponin complex to tropomyosin
Troponin T
inhibits actin-myosin binding
Troponin I
calcium binding protein
Troponin C
- contain myosin and actin
- contain the entire length of the thick filament
A Band
- contain the remaining thin filament
I Band
- Tethers Myosin to Z lines (scaffolding)
- Binds Z lines to M line
Titin
- Attaches to plasmalemma
- Stabilizes plasmalemma and prevents contraction-induced rupture
Dystrophin
Binds Actin to Z lines
Actinin and Capz Protein
Binds Z lines to plasma membrane
Desmin
- Involves motor neurons and extrafusal fibers
- Demonstrated by the Sliding Filament Model
Skeletal Muscle Contraction
- Thin filaments “slides” against the thick filaments towards the center of the sarcomere
- Z-discs meets the myosin filaments
Sliding Filament Model
if activated, this receptor would activate RYANODINE RECEPTOR (a calcium release channel)
Dihydropyridine Receptor
it would sequester the Calcium back once the action potential is gone
Calsequestrin
Force to cause the contraction
Power Stroke
Mutation in dystrophin in the heart
Dilated Cardiomyopathy
What is the distance achieved in each cross-bridge cycle?
10 nanometer
- Brief muscular contraction followed by relaxation
- due to a single action potential
- Starts 2 millisecond after depolarization of the membrane
- Duration: 7.5 ms in “Fast” Fibers; 100 ms in “Slow” Fibers
Muscle Twitch
- All muscle fibers innervated by a single motor nerve fiber
o Made up of alpha motor neuron, its axon and all muscle fibers it supplies
o Alpha motor neurons are also called “final common pathway”, “lower motor neuron” - For movements that require rapid and exact control
o One motor nerve fiber would innervate few muscles
The Motor unit
Large amount of ATP are cleaved to form ADP during contraction process, and the greater the amount of work performed by the muscle, the greater the amount of ATP that is cleaved; this phenomenon is called _____
The Fenn Effect
Muscle contraction is said to be ___ when the muscle does not shorten during contraction
Isometric
Muscle contraction is said to be ___ when the muscle does shorten but the tension on the muscle remains constant throughout the contraction
Isotonic
- means adding together of individual twitch contractions to increase intensity of overall muscle contraction
Summation
- Type of summation that occurs by increasing the number of motor units contracting simultaneously
- size principle is followed
- Motor units driven asynchronously by the spinal cord
- Contraction alternates among motor units one after the other
Multiple Fiber Summation (Spatial Summation)
Type of summation that occurs by increasing the frequency of contraction and sometimes can lead to TETANIZATION
Frequency Summation (Temporal Summation)
- Smaller motor units are recruited first before big motor units
- Basis: small motoneurons in the spinal cord are more excitable than large ones
Size Principle
When the frequency reaches a critical level, the successive contractions eventually become so rapid that they fuse together and the whole muscle contraction appears completely sooth and continuous. This process is called ___
Tetanization
- Each contraction occurs after complete relaxation, its initial strength of contraction may be as little as one half its strength
- Each contraction increases up to plateau
- Due to Ca++ accumulation, increase in temperature, ph changes
- Seen in warm-up exercise
Staircase Effect or Treppe
- Complete relaxation not given; subsequent stimuli done
Results in progressive increase in total contraction strength
Wave Summation
- no relaxation after contraction
Complete Tetany
incomplete relaxation after contraction
Incomplete Tetany
Which of the following tetanizes at lower stimulus frequency?
Slow-Twitch Fibers
Which of the following has a larger maximal force during tetany?
Fast-Twitch Fibers
Tension developed by stretching the muscle to different lengths
Passive Tension
The tension developed when the muscle is stimulated to contract at different lengths.
Active Tension
Active Tension + Passive Tension
Total Tension
If the resting muscle length is extended, the following will happen:
Passive Tension: Increases
Active Tension: Decreases
Force of Contraction: Increases
- With zero load, shortening velocity is maximal
Corresponds to the maximal cycling rate of the cross-bridge - Increasing the load, decreases the velocity of the muscle shortening
Force-Velocity Relationship
- Reflects work done at each load
- Maximal rate of work done at a submaximal load (when force of contraction is approximately 30% of the maximal tetanic tension)
Power-Stress Curve
- Length is held constant
- No muscle shortening/lengthening
E.g. holding an Ipad in midair
Isometric Contraction
- Load is held constant
- With Muscle Shortening: CONCENTRIC CONTRACTION (e.g.pulling a weight up)
- with muscle lengthening: ECCENTRIC CONTRACTION (e.g. lowering a weight down)
Isotonic Contraction
- Remaining contractile activity of the muscle at rest
- Due to low levels of contractile activity in some motor units driven by reflex arcs from muscle spindles
- Helps maintain posture
Muscle Tone
- Protective mechanism to prevent muscle cell injury or death
- Directly proportional to rate of depletion of muscle glycogen and creatine phosphate stores and the accumulation of lactic acid
- Occurs earlier in fast-twitch fibers
Muscle Fatigue
- increase of the total mass of a muscle
- Maybe due to be due to fiber hypertrophy or sarcomere addition
Muscle Hypertrophy
- total mass is decrease
- Seen in denervation
- when a muscle remains unused for many weeks, the rate of degradation of contractile proteins is more rapid than the rate of replacement
Muscle Atrophy
- increase in the number of actin and myosin filaments in each muscle fiber, causing enlargement of the individual muscle fibers
Fiber Hypertrophy
- actual number of muscle fiber has been observed to increase in addition to the fiber hypertrophy
Fiber Hyperplasia
The fibrous tissue that replaces the muscle fibers during denervation atrophy also has a tendency to continue shortening for many months, which is called ___
Contracture
o Will have Muscle Fasciculation
- Small, irregular contractions (due to Ach release from degenerating axons)
o Will have Muscle Fibrillation
- Spontaneous, repetitive contractions (Cholinergic receptors spread out over entire cell membrane)
o Function may fully return w/in 3 months due to Reinnervation
o No further return of function after 1-2 years
o Replaced by fibrous-fatty tissue
Muscle Denervation
Remaining nerve fibers sprout new axons (innervate many paralyzed muscle fibers) -> macromotor units -> muscles become stronger but w/less control
Poliomyelitis
- several hours after death, all the muscles of the body will go into a state of contracture
- the rigidity results from loss of all ATP (required to cause separation of cross-bridges from the actin filaments during the relaxation process)
- Start after 3-6 hours
- End after 15-25 hours; earlier in high temp
Rigor Mortis
Anti-Ach receptor antibodies
Myasthenia Gravis
- milder form of dystrophy
- is also caused by mutations of the gene that encodes for dystrophin but has later onset and longer survival
Becker Muscular Dystrophy
Skeletal muscle fibers are innervated by large, myelinated nerve fibers that originate from large motoneurons in the ____
Anterior horns of the Spinal Cord
A junction between a single axon terminal and the muscle fiber membrane. The invaginated membrane is called the ____
Synaptic gutter or synaptic through
A space between the terminal and the fiber membrane is called the ___
Synaptic space or synaptic cleft
at the bottom of the gutter are numerous smaller folds of the muscle membrane called ____
Subneural clefts
- neurotransmitter that excites muscle fiber membrane
- synthesize in the cytoplasm terminal, but is absorbed rapidly into many small synaptic vesicles
Acetylcholine
- found in the synaptic space
- enzyme which destroys acetylcholine a few milliseconds after it has been released from the synaptic vesicles
Acetylcholinesterase
- initiates an action potential that spreads along the muscle membrane and thus creating muscle contraction
End plate potential
drugs that stimulate the muscle fiber by Ach like action
Metacholine, Carbachol, Nicotine
drugs that stimulate the neuromuscular auction by inactivating acetylcholinesterase
Neostigmine, Physostigmine, Diisipropyl flurophosphate
- smooth muscle cells contain a large amount of another regulatory protein called ___
- this protein initiates contraction by activating the myosin cross-bridges
Calmodulin
Special mechanism in the heart cause a continuing succession of heart contraction
Cardiac rhythmicity
- dark areas crossing the cardiac muscle fibers
- cell membranes that separate individual cardiac muscle cells from one another
Intercalated discs
- Exhibits atrial and ventricular Syncitium (contract together)
- Uses EXTRAcellular and INTRAcellular Calcium
- Atrial and Ventricular AP is different form Conductive
System AP (SA Node)
Cardiac Muscle Contraction
- More developed T-tubule, Less Developed SR compared
to skeletal Muscles - Calcium Regulation of Cardiac muscles
1. Calcium Channels (increases intracellular
calcium)
a. L-Type or Slow Calcium Channel ->predominant; voltage-gated
b. Fast calcium channel
2. 3Na+-1Ca++ Exchanger (decreases
intracellular calcium)
3. Ca-ATPase pump (decreases intracellular
calcium)
Cardiac Muscle Contraction
Cardiac Muscle vs Skeletal Muscle
Cardiac Muscles: Electrochemical Coupling (Ca++-
induced release of Ca++)
Skeletal Muscles: Eletromechanical Coupling
(interaction between DHPR and RYR)
Cardiac Muscle vs Skeletal Muscle
Cardiac Muscles: T-tubules in the Z lines
Skeletal Muscles: T-tubules at the ends of I-bands
Cardiac Muscles: Syncitium, No Tetany (Due to long refractory period secondary to voltage-gated L-type Calcium Channels)
Skeletal Muscles: Recruitment, may undergo tetany
- No troponin
- Contains the following: MLCK (Myosin Light Chain Kinase); Calmodulin; Caldesmon, Calponin
- MYOSIN-based regulation
- Contains DENSE BODIES (Similar to z discs)
SARCOPLASMIC RETICULUM (SR) - rudementary (smooth muscle rely on extracellular Calcium
Smooth Muscle Contraction
- Rudimentary t-tubules
- Contains Voltage-gated L-type Ca++
Channel And The 3Na+-1Ca++
Antiporter
Caveoli
- Desmin and Vimentin
- Connect dense bodies with cytoskeletal network
Intermediate Filament
- Opens slowly and remains open much longer
- Used by hormones, NT
InsP3-gated Ca++ channel
- Causes relaxation vascular smooth muscles
- Used by Nitric Oxide, Adenosine, drugs, hormones
cAMP & cGMP mechanisms
Sponteneous elevation in intracellular calcium levels
Ca++ “sparks”
- Uses much less ATP
- Slow onset but prolonged time for contraction
“Latch” State: force of contraction maintained with low
energy expenditure (300x less than skeletal muscles) during tonic contraction - Greater force of contraction (4-6 kg/cm2)
- May produce connective tissue (e.g. atherosclerosis)
Smooth Muscle
Cardiac Muscle Action Potential
Phase 0: Rapid Depolarization - Sodium Influx
Phase 1: Initial Repolarization - Partial efflux of K
Phase 2: Plateau - influx of Ca+2
Phase 3: Final repolarization - Complete potassium influx
Phase 4: Resting - slightly more than influx of K
Which are the one that increases Calcium?
- L Type
- Calcium ATPase
- Calcium Sodium Antiport
♣ output from the CNS travels along two pathways that are anatomically and functionally distinct
Nervous System
α-motor neuron links CNS to skeletal muscles
Somatic Motor Neurons (SNS)
autonomic neurons links CNS to visceral organs
Autonomic Motor Neurons (ANS)
ANS and SNS are organized on the basis of the reflex arc, composed of:
afferent limb
integrating center
efferent limb
afferent fibers from visceral structures reach CNS via ___
autonomic pathways
visceral afferents are found in the:
CN 7, 8, 9 and 10 (VAGUS nerve is the most parasympathetic
Pathway: SINGLE NEURON PATHWAY
Neurons involved: ALPHA-MOTOR NEURONS (large diameter, myelinated, rapidly conducting
Effector: SKELETAL MUSCLE
Innervation of effector: skeletal muscle innervated by single neuron
Neurotransmitter: Ach only
Somatic Nervous Sytem
Effect of NT: release of Ach (contraction of skeletal muscle)
Location: NEUROMUSCULAR JUNCTION
Location of NT synthesis and storage: AXON TERMINAL
Postsynaptic receptors: NICOTINIC RECEPTOR (N1) at Motor End Plate (MEP)
Somatic Nervous System
Pathway: TWO WAY NEURON PATHWAY
Neurons involved: PREGANGLIONIC - small diameter, myelinated, slow conducting B fibers
POSTGANGLIONIC - small diameter, unmyelinated C fibers
Effector: VISCERAL stuctures
Innervation of effector: VISCERAL effectoe may be innervated by many postganglionic neurons
Neurotransmitter: Ach, NE, Epi, Dopamine
Autonomic Nervous System
Effect of NT: response may be INHIBITORY of EXCITATORY
Location: NEUROEFFECTOR JUNCTION
Location of NT synthesis and storage: BEADS or VARICOSITIES that line the branching networks of postganglionic neurons
Postsynaptic receptors: postsynaptic receptors widely distributed on the target tissues
no specialized region of receptors like the MEP
Autonomic Nervous System
- part of the nervous system responsible for homeostasis
- regulatory in function
- essentially motor
- without ANS, survival is possible but the ability to adapt to stressors from the environment will be severely compromised
- striking characteristics - rapidity and intensity with which it can change visceral functions
Autonomic Nervous System
- can increase HR to 2x normal within 3-5 secs.
- can double ABP in 10-15 secs.
- can cause sweating within secs. operates through visceral reflexes
Autonomic Nervous System
Most of the organs are parasympathetically innervated except for _____
Sweat glands, blood vessel
Classification of the ANS
Anatomic differences
Functional differences
Biochemical differences
Pharmacologic differences
Divisions of ANS Based on Anatomic Differences
- Sympathetic NS
- Parasympathetic NS
- Enteric Nervous System / Intramural Nerve Plexus of GIT
- “mini brain” because it contains all elements of nervous system
- sensory and motor neurons, and interneurons (plexuses)
- can function autonomously but normal GI function often requires communication between the CNS and the ENS
- confined within GIT walls
- two divisions:
Myenteric or Auerbach’s Plexus - contraction of smooth muscle
Meissner’s or Submucosal Plexus - secretion
Enteric Nervous System
- Thoracolumbar Outflow
- larger division
- prepares individual to cope with emergency
- ensures that the body can respond appropriately to a stressful or emergency situation
- concerned with mobilizing the person for “fight or flight”
Symphathetic Nervous Sytem
♣ mydriasis ♣ increased ABP ♣ vasoconstriction ♣ increased in skeletal muscle strength ♣ increased ventilation
Symphathetic Nervous Sytem
♣ decreased GIT activity
♣ elevation of plasma glucose and fatty acid levels
♣ increase in mental activity
♣ lowers threshold in the reticular formation
♣ redistribution of blood from skin and splanchnic regions towards skeletal muscle
Symphathetic Nervous Sytem
a neuroendocrine organ
Adrenal Medulla
2 reasons why adrenal medulla is considered to be part of the ANS
- Nerve supply to AM is anatomically and biochemically identical to autonomic preganglionic nerve fibers
- Adrenomedullary cells are embryologically, anatomically and functionally identical to postganglionic autonomic nerve fibers
2 reasons why adrenal medulla is considered a component of SNS and not PSNS
- Origin of nerve supply of AM is thoracolumbar
- Adrenomedullary cells secrete catecholamines
Epinephrine – 80%
Norepinephrine – 20%, the neurotransmitter of sympathetic nerves
- Craniosacral Outflow
- dominates in quiet, relaxed situation
- activity tends to conserve energy and restore the body’s resources (anabolic nervous system)
Parasympathetic Nervous System
- cranial outflow supplies the visceral structures in the head through CN 3, 7 and 9 and the structures in the thorax and upper abdomen through CN 10
- sacral outflow supplies pelvic viscera through pelvic branches of the 2nd to 4th spinal nerves
Parasympathetic Nervous System
Origin of preganglionic neuron: CRANIOSACRAL
Location of peripheral ganglia: TARGET ORGAN
Length of preganglionic fiber: LONG
Length of postganglionic fiber: SHORT
Degree of branching of preganglionic nerve: LESS BRANCHING
Parasympathetic Nervous System
Origin of preganglionic neuron: THORACOLUMBAR
Location of peripheral ganglia: PARAVERTEBRAL
Length of preganglionic fiber: SHORT
Length of postganglionic fiber: LONG
Degree of branching of preganglionic nerve: MORE BRANCHING
Sympathetic Nervous System
Nature of activity: Dominates in emergency (“fight or flight”) situations
Energy utilization: Involves expenditure of energy (catabolic)
Response: appropriate to emergency and stress situations; synchronized and coordinated
Range of Effect: Affects widespread regions of the body (“mass discharge”)
Sympathetic Nervous System
Fiber Connections: Due to divergent connection (1:20)
Branching of preganglionic fibers: Preganglionic fibers branch extensively
Neurotransmitters: Catecholamines secreted by adrenal medulla are distributed to all regions of the body through circulation
Duration of Response: Sustained duration due to slow deactivation of norepinephrine (active reuptake)
- Norepinephrine lingers in the synaptic cleft for a longer time than acetylcholine
- Effects triggered by adrenergic neurons are longer lasting
Sympathetic Nervous System
Nature of activity: Dominates in quiet, relaxed situations
Energy utilization: Tends to conserve energy (anabolic) and restores the body’s resources
Response: favors digestion and absorption of food ( activity of intestinal muslces, intestinal secretion)
Range of Effect: Discrete, selective and limited
Localized to a single organ
Parasympathetic Nervous System
Fiber Connections: Manner of fiber connection is 1:1 or 1:2
Branching of preganglionic fibers: Limited branching of preganglionic fibers
Neurotransmitters: Usually no acetylcholine in circulation
Duration of Response: Short duration due to fast deactivation of acetylcholine (enzyme hydrolysis by acetylcholinesterase)
Parasympathetic Nervous System
- Exert opposite effects but operate reciprocally to produce coordinated responses
- The 2 divisions can also act in a synergistic or cooperative manner
Dual Innervation
SYMPATHETIC only
sweat glands
adrenal glands
most blood vessels
pilomotor muscle
PARASYMPATHETIC only
lacrimal muscle (tear glands) ciliary muscle (accommodation for near vision)
Parasympathetic transmitter
Acetylcholine
Synpathetic transmitter
Norepinephrine
2 tissue enzyme that can cause destruction of norepinephrine
- Monoamine oxidase (found in the nerve endings)
- Catechol-O-methyl transferase (present diffusely in the tissues)
Binding of norepinephrine with its receptor increases the activity of the enzyme adenylyl cyclase which causes formation of ___
Cyclic adenosine monophosphate (cAMP)
Acetylcholine activates two types of receptors which are called
Muscarinic
Nicotinic receptors
- A receptor which uses G protein as their signaling mechanism
- found on all effector cells that are stimulated by the postganglionic cholinergic neurons
Muscarinic receptors
- are ligand-gated ion channels found in autonomic ganglia at the synapses between the preganglionic and postganglionic neurons of both PNS and SNS
- are also present at many nonautonomic nerve endings
Nicotinic receptors
Alpha receptor and function
Vasoconstriction Iris dilation Intestinal relaxation Intestinal sphincter contraction Pilomotorcontraction Bladder sphincter contraction Inhibits neurotransmitter release (alpha1)
Beta receptor and fuction
Vasodilation (b2) Cardioacceleration (B1) Increased myocardial strength (B1) Intestinal and uterus relaxation (B2) Bronchodilation (B2) Calorigenesis (B2) Glycogenolysis, bladder wall relaxation (B2) Lipolysis (B1) Thermogenesis (B3)
A synthetic hormone chemically similar to epinephine and norepinephrine that has extremely strong action on B receptors but no action on A receptors
Isopropyl norepinephrine
Parasympathetic exitation contracts ___ which releases the tension on the ligaments and allow the lens to become more convex causing eye to focus near at hand.
Ciliary muscle
The nasal, lacrimal, salivary and many gastrointestinal glads ares strongly stimulated by ___, usually resulting in copious quantities of watery secretions.
Parasympathetic nervous system
Gland of the small and large intestines are controlled principally by local factors in the intestinal tract itself and by ___
Intestinal enteric nervous system
Synthesis and Storage: Acetylcholine (Parasympathetic)
Acetyl Coa + Choline -> Acetylcholine (choline acetyltransferase)
- synthesized in the cytoplasm of axon terminal by acetylation
- stored as clear round vesicles
choline comes from the ECF and enters the axon terminal by active transport - acetyl-CoA and ATP provided by mitochondria
- choline acetyltransferase synthesized in the soma and brought to axon by axoplasmic transport
Synthesis and Storage: Norepinephrine (Sympathetic)
- synthesized from the amino acids phenylalanine and tyrosine
Phenylalanine -> Tyrosine (phenylalanine hydroxylase)
Tyrosine -> DOPA or dyhydroxy phenylalanine (tyrosine hydroxylase)
DOPA -> Dopamine (DOPA decarboxylase)
In the adrenal medulla, ____ catalyzes the conversion of norepinephrine to epinephrine.
phenylethanolamine-N-methyltransferase (PEMT)
undergoes enzymatic destruction via acetylcholinesterase diffusion
Acetylcholine
undergoes active reuptake by the prejunctional junctional fiber diffusion into the extracellular spaces
Norepinephrine
enzymatic destruction of NE (Norepinephrine) while it is still in the synaptic cleft
catechol-ortho-methyltransferase (COMT)
enzymatic destruction of NE while it is still in the axoplasm of the preganglionic fiber
monoamine oxidase (MAO)
Location: cell bodies of postganglionic neurons
effector organs
Mechanism of Action
when a NT binds with receptor → causes a conformational change in the structure of the protein molecule → the cell may either be activated or inhibited
Autonomic Receptors
How do NTs work?
by causing a change in membrane permeability to various ions
- have affinity for nicotine (small amounts)
- excess nicotine acts as a blocking agent by persistent depolarization
- sites: MEP, all autonomic ganglia, chromaffin cells of AM
- types: N1 and N2
Nicotinic Receptor
Differences between Nicotonic receptors in MEP and autonomic ganglia
- both activated by the agonist Ach, nicotine, and carbachol
- both antagonized by curare
- hexamethonium, an antagonist, blocks N2 receptors but not N1
- hexamethonium produces vasodilation can be used for the treatment of hypertension
- have affinity for muscarine (a mushroom poison when introduced into the body can mimic ACh on particular sites)
sites: effector cells activated by PS; effector cells activated by S cholinergic
Muscarinic Receptors
Types of Muscarinic Receptors
M1 - enhances gastric acid secretion
M2 - most abundant in the heart, smooth muscle in intestine, uterus, trachea, bladder
Mechanism of action: binding of agonist to M2–> inhibits adenylcyclase
M3 - smooth muscle of airways
Mech of action: formation of IP3 (inositol 1, 4, 5 triphosphate) and DAG(Diaglycerol) and increase in intracellular calcium
M4 - pancreatic acinar cells and islet tissue
M5 - sphincter muscle of iris, esophagus, parotid gland, cerebral blood vessel
are of the indirect ligand G protein linked type
Adrenoceptors
Types of Adrenoceptors
Alpha 1 Receptors Alpha 2 Receptors Beta 1 Receptors Beta 2 Receptors Beta 3 Receptors
- location: radial muscle of iris; blood vessels of skin (vasoconstriction); sphincters of GIT and bladder
- antagonist: Prazosin
- mechanism of action: - involves a G protein (Gq) activate phospholipase C and increase the intracellular concentration of IP3
Alpha 1 Receptors
location: presynaptically (autoreceptors) inhibit release of NE ; GIT walls
selective antagonist: Yohimbine
Mechanism of Action: - involves Gi protein act through inhibition of adenylyl cyclase → decreased cAMP levels
Example:
activation of alpha 2 receptors in GIT wall → relaxation
Alpha 2 Receptors
location: prominent in the heart, salivary glands, adipose tissue, kidneys (promote renin secretion)
Mechanism of Action: involves Gs protein activation of adenylcyclase to increase cAMP concentration
Beta 1 Receptors
sites: predominate in smooth muscle of airways, blood vessels of skeletal muscles (vasodilation), GIT and bladder walls
Mechanism of Action: same as beta 1
- involves Gs protein activation of adenylyl cyclase to increase cAMP concentration
Beta 2 Receptors
- present on cells of brown adipose tissue
- activation causes thermogenesis (heat production)
Beta 3 Receptors
a drug that binds to the receptors for a neurotransmitter and that promotes the processes that are stimulated by that NT is said to be an agonist of that NT
Agonist
a drug that blocks the action of a NT
Antagonist
- autonomic and somatic reactions work together to maintain essential body states and to effect necessary adaptation
- levels of autonomic integration within the CNS are arranged in a hierarchy
- CNS controls the activity of the ANS shows hierarchy in the control mechanism
Central Control of Autonomic Functions
- simple reflexes like contraction of a full bladder are integrated in the spinal cord
transection of the spinal cord»_space; spinal shock»_space; absence of reflexes, low ABP
Spinal Cord
- center for the regulation of the ANS
- called by Sherrington, “the HEAD GANGLION,” of the ANS because stimulation of this produces autonomic responses
sympathetic: posterior center
parasympathetic: anterior center - integrates somatic, autonomic and endocrine functions
- mediates those reactions that maintain homeostasis
Hypothalamus
- unit that regulates emotional and instinctual behavior
- concerned with the following: regulation of feeding behavior; expression of rage and fear; control of sexual behavior
Limbic System
- refinement of control over the autonomic and somatic reactions
- examples: tells whether emotion is pleasant or unpleasant; responsible for voluntary control of respiration
Cerebral Cortex
- Where centers for regulation of cardiovascular and respiratory centers are located
- The medullary areas for the autonomic control of the CVS and respiratory system are called the vital areas because damage to them is fatal
- Deglutition, coughing, sneezing, gag reflex, vomiting reflexes are integrated in the medulla
- EXAMPLES: respiratory center, vasomotor center, swallowing center, vomiting
Medulla Oblongata
those that control pupillary responses to light are integrated in the ____
Midbrain
Muscarinic receptor in brain (presynaptic neuron) and enhances gastric acid secretion
M1
- most abundant in the heart
- smooth muscle in intestine, uterus, trachea, bladder
- mechanism of action: binding of agonist»inhibits adenylcyclase
M2
- smooth muscle airways
- mechanism of action: formation of IP3 (inositol 1,4,5 triphosphate) and DAG (diaglycerol) and increase in intracellular calcium
M3
-muscarinic receptors found in pancreatic acinar cells and islet tissue
M4
Muscarimic receptor for sphincter muscle of iris, esophagus, parotid gland, cerebral blood vessel
M5
