final Flashcards
3 types of muscle
- development of skeletal muscle
- Skeletal muscle – makes up muscular system
a. Includes diaphragm
b. Multinucleated – more than one nucleus per cell
- During development – many muscle cells fuse; contain multiple nuclei as a result
c. Striated – due to proteins/filaments
d. Long, stacked in parallel
- each individual muscle cell/fibre is long and skinny
- many are stacked together – go from one end to the other end of the muscle - Cardiac muscle – found only in the heart
a. Uninucleated
b. Striated – dark and light bands
c. Don’t only lay parallel – also stacked end to end
- joined via intercalated disk – region where one cardiac muscle cell contacts other at end - Smooth muscle – appears throughout the body systems as components of hollow organs and tubes
a. Key component of blood vessels – allows them to contract
b. Uninucleated
c. Not striated
d. Sheets or tubes – often spindle shaped; not as long as skeletal muscle cells
Muscle contraction allows
Classifications
Muscle contraction allows
- Locomotion – movement of joints, limbs and whole body
- Propulsion of contents through various hollow internal organs – movement of blood through the circulatory system; food through digestive system
- Emptying of contents of certain organs to external environment – sphincters act as valves; allows defecation and urination
Classified as either
- Striated or unstriated (better)
- Voluntary or involuntary
2 neuron chain of NMJ
Upper Motor Neurons – cell body in the motor cortex; synapse on LMN in the spinal cord
• Approx. 90% desiccate in the medulla – primary neurons on right side control left body
Lower Motor neurons – cell body in ventral root spinal cord; axons synapse on muscle cells
a. Activation of lower motor neuron causes contraction of muscle cells
• Neuromuscular junction
b. Motor unit – the group of muscle cells controlled by one LMN
i. Mammals – each muscle cell receives only one synapse
• Always excitatory – Ach
• LMN – can innervate one (more rare) or many muscle cells (more common)
ii. Other vertebrates – can have 2 synapses
NMJ differences
- summation
Very large
• NMJ – 1000 μm2
• Central synapse – 0.05 μm2
Highly folded – increases surface area
a. Crests – high density of nicotinic AChR (hundreds of thousands)
• High density causes large EPSP
b. Troughs – lots of voltage gated Na+ channels
Causes large EPSP – approx. 30-50mV (central synapse is approx. 0.5-1mV)
• always enough to stimulate opening of Na+ channels & fire AP
A single AP of LMN is always enough to cause AP in muscle cell
• No summation of EPSP – excitation will always result in contraction
• High safety factor
Structure of muscle
Consists a number of muscle fibers (cells) lying parallel to one another and held together by connective tissue
- Tendon – end of muscle; tough CT
- Muscle fascicle – bundle of cells/fibres within muscle; surrounded by CT
- Single skeletal muscle cell is known as a muscle fiber
a. Large, elongated, and cylindrically shaped
b. Fibers usually extend entire length of muscle
Structure of muscle cells
a. Multinucleated
b. Myofibrils – bundles of contractile proteins within cell
c. Sarcoplasmic reticulum – specialized endoplasmic reticulum; surrounds myofibril
• Always sits with middle in the middle of the sarcomere (middle of H zone)
• Stores Ca2+ ions
d. Sarcolemma – membrane of muscle cell
e. T-tubules – form a mesh of canals through muscles
• Have openings through sarcolemma
• Lie adjacent to & sits between sections of SR
Structure of myofibril
- proteins of M line!
- Sarcomere – z line to z line
• M line – middle of H zone
• Only thick filaments at rest
• A band – length of thick filaments - Thick filaments
a. Mainly myosin – protein molecule; 2 identical subunits shaped like golf club
i. Tail ends – intertwined around each other
• Oriented towards center of filament
ii. Myosin heads – globular ends project out from hinge at regular intervals
• Form cross bridges between thick and thin filaments
iii. 2 binding sites – critical to contraction
• Actin binding site
• Myosin ATPase
iv. A motor protein – hydrolyses ATP to convert chemical energy to carry out mechanical work - Thin filaments
a. Actin – primary structural component of thin filaments
• G-actin monomers are spherical – assemble into long chains
• Each actin molecule has a special binding site for attachment with myosin head
b. Tropomyosin – threadlike molecules; interact with actin along its spinal grove
• Covers myosin binding site
c. Troponin
i. 3 polypeptide units
• One binds to tropomyosin
• One binds actin
• One binds with Ca2+
ii. Unbound – troponin stabilizes tropomyosin ni blocking position
iii. Bound – tropomyosin uncovers binding site; allows formation of cross bridges & contraction
d. Nebulin – runs along the middle of actin ball chains & aligns actin filaments - Titin – giant elastic protein
a. Joins M-lines to Z lines at opposite ends of sarcomere – the whole length of sarcomere
b. Two important roles:
• Helps stabilize position of thick filaments in relation to thin filaments – keeps the thick filaments in the middle of thin filaments
• Improves muscle’s elasticity – sarcomere can get longer and shorter - Myomesin – main protein of M line
• Structural element – keeps thick filaments at regular intervals
Excitation Contration coupling
- sliding filament hypothesis
- process
- what bands are t-tubule and SR on
- do actin and myosin contract
- what happens to Ach
- calsequesterin!!
Sliding filament hypothesis – muscle shortens when actin and myosin slide past each other
Process
1. AP from LMN – causes release of Ach into synaptic cleft of NMJ
- ACh binds to the receptor – nicotinic AChR
a. Allows entry of Na+ through voltage gated channels
b. Causes EPSP large enough to trigger an AP – AP travels across membrane of cell - AP invades the T-tubule system – continuous with sarcoplasm
a. T-tubule – run perpendicular from surface of muscle cell into central portions of fibres
i. Aligned on edges of A band – directly adjacent to thick myofilaments/myosin
b. Causes voltage gated dihydropyridine (DHP) receptors to open – channel within t-tubule; blocked by dihydropyridine drug
i. Allows for small amount of Ca2+ to enter into cell
c. DHP is connected to RyR channel via RyR foot – piece of globular protein
i. Ryanodine receptor – channel within SR; blocked by ryanodine drug
- Physically pulled open
- Opening causes a massive release of Ca2+, and increase in intercellular Ca2+ concentration - Ca2+ binds troponin
a. At rest – myosin head is cocked in the absence of Ca2+
i. Tropomyosin is blocking the binding of myosin to actin – only weakly bound to actin
b. Binding of Ca2+ to troponin molecules – pulls tropomyosin away from binding sites on actin
i. Allows myosin to bind to actin
ii. Power stroke – cross bridges bend
- Myosin heads move thin filaments towards M line – releases Pi
- End of power stroke – releases ADP; tightly bound in rigor state
iii. Cross bridges release when ATP binds
- Hydrolyzation of ATP to ADP + Pi – energy allows cocking of myosin head
- Weakly bound to myosin at this stage
- Can binds to more distal actin site as long as Ca2+ is available to bind tropomyosin
- Repeating cycle shortens sarcomere – actin filaments slide closer to M line
c. Causes contraction of sarcomere – actin and myosin DO NOT contract - When AP stops arriving at NMJ
a. Ach dissociates from receptor & is degraded by AChE
i. Choline is recycled back into synaptic terminal
b. Free Ca2+ pumped back into SR from cytosol via ATPase – powerful ATPase transporter
i. Calsequestrin protein – binds Ca2+ and helps sequester
ii. Ca2+ dissociates from troponin – pumped into SR
c. Tropomyosin moves back in front of binding sites
i. Muscle is unable to maintain tension
d. Actin and myosin slip past each other
i. Pulled apart by titin & antagonistic muscle (ex. triceps contracting will cause stretching of bicep sarcomeres)
Rigor Mortis
Rigor state – myosin head is tightly bound to actin site; release via binding of ATP to myosin
a. ATP -> ADP + Pi causes reactivation of myosin head into cocked position – ready to bind again
- Will continue to bind as long as Ca2+ is available and will continue to shorten the muscle
~3-4 hours after death, peak at ~12 hours – muscle becomes very stiff
a. SR becomes leaky – intracellular Ca++ rises
b. Ca++ allows troponin-tropomyosin complex to move aside and allow myosin cross bridges to bind to actin.
• Release of ADP and Pi results in rigor state binding
c. Dead cells do not produce ATP – cross bridges cannot detach
Rigor mortis subsides when enzymes start to break down myosin heads
– Muscle is starting to break down
Energy use in muscles
- Splitting of ATP by myosin ATPase for power stroke
- Active transport of Ca2+ back into sarcoplasmic reticulum
a. Ca2+ ATPase pumps - Na+/K+ ATPase
a. Neurons and muscle cells need to maintain RMP in order to generate AP
Main energy sources for muscle contraction
- bloodflow requirements
- enzyme requirements
- what type of exercise
- Stored ATP (very little stored) – only have enough stored for a few seconds worth of activity; up to a minute
- Creatine phosphate – first energy storehouse tapped at onset of contractile activity
a. Creatine kinase – enzyme catabolizes bidirectional transfer between ATP and creatine
b. At rest – ATP demand is low
i. Creatine kinase transfers Pi from ATP to creatine
- Creatine phosphate = phosphorylated creatine
ii. Allows storage of energy as creatine phosphate
c. When energy is needed
i. Creatine kinase phosphorylates ADP from Pi on creatine
- ATP is used for contraction
- Provides 4-5 times the energy of stored ATP
- Limited supply (only a few minutes)
Most energy for long term sustained contraction comes from oxidative phosphorylation and anaerobic glycolysis
- Oxidative phosphorylation – takes place within muscle mitochondria if sufficient O2 is present
a. Provides energy during light to moderate exercise
b. Uses stores of glycogen in muscle (30 min) – depolymerizes to glucose
i. Good yield of ATP – 38 per glucose molecule
c. Aerobic exercise – requires adequate supply of oxygen
i. Increased blood flow via
- Increase ventilation
- Increase heart rate and force of contraction
- Dilate skeletal blood vessels - Anaerobic Glycolysis – primary source of ATP when o2 is low
a. Supports anaerobic & high-intensity exercise – oxygen supply is limited
b. Rapid supply of ATP
- Only a few enzymes involved – fewer enzymes than in oxidative phosphorylation
c. Very low ATP yield – only 2 ATP per glucose molecule
- Lactic acid – acidifies muscle and contributes to fatigue
- Duration of anaerobic glycolysis is limited
Causes of muscle fatigue
Central fatigue
a. Psychological
• “I just can’t” – differs person to person
• Plays larger role for elite athletes
Peripheral – plays larger role in majority of population; physiologists are unsure which is most important
a. Decrease in release of ACh from LMN with sustained activity
b. Receptor desensitization – when receptors are repeatedly exposed, they can lower affinity for ligand
c. Changes in of muscle RMP
• If muscle is very active – firing a lot of AP
• Eventually – you will see slight changes in ECF K+
• Causes depolarization of cells – can lead to inefficiency
d. Impaired Ca2+ release by SR – RyR may not be as effective at allowing Ca2+ into cell
e. Intracellular pH of muscle – due to lactic acid from anaerobic activity
f. Others….
Generation of tension
- timing of AP in neuron vs muscle cell
Electrode in motor neuron & in muscle cell – allows us to see timing of events
AP arrives from LMN
a. AP in muscle cell approx. 2 ms after neuronal AP
Tension generated in muscle – experiences lag
a. Latent period – due to:
• AP propagating in muscle
• Opening of DHR and RyR receptors – flooding of Ca2+
• Interaction of Ca2+ with myosin heads – pulling of tropomyosin away
b. Contraction phase
c. Relaxation phase
Types of stimulation
- Simulation at low frequency – muscle cell generates tension and relaxes
- Stimulation at higher frequency – stimulating muscle cell before it’s relaxes
a. Analogous to GP summation – can generate tension before single twitch has been allowed to relax - Summation leading to unfused tetanus
a. Stimulating repeatedly before relaxation – stimulated to maximum tension
b. Max tension – point of tetanus
- Unfused – still getting to relax slightly from one pulse to the next - Summation leading to complete tetanus – stimulated too quickly to get opportunities to start to relax
a. This is the most amount of tension that a muscle cell can generate
- Maximum tension is usually higher than unfused tetanus
Maximum tension
- 2 theories
requires several AP to occur; 2 theories (both likely contribute)
- Some think it takes several APs to increase intracellular Ca++ enough to saturate actin’s myosin binding sites
a. The concentration of Ca2+ doesn’t get high enough with single AP - Some think intracellular Ca++ reaches its maximum (saturates) after first action potential.
a. Summation and Tetanus develop because sustained elevation of increased Ca++ allows greater exposure of actin binding sites and therefore maximizes interaction with myosin (effect is time dependent)
b. More time dependent than concentration dependent
Length tension
the amount of tension a muscle can generate depends on initial resting state
Optimal resting length – we can generate the most tension from fibre when thin filaments only overall until the end of the myosin heads (medium amount of overlap)
Stretching – less overlap; muscle cell can’t generate as much tension because there’s not as many myosin heads able to interact with actin
Compressed – pushing thin filaments towards m line; can’t generate as much tension because contracted sarcomere has many proteins within cell
o All the other molecules start to push against each other – work against the generation of tension
Types of skeletal muscle fibres
- chickens vs mammels
- 3 types & features!
- In chickens and turkey – fibres are grouped together
o White meat – white muscle
o Dark meat – red muscle - Mammals – fibres are interspersed
o Different fibre types may coexist side by side
3 types of motor fibres/units – all muscle fibres within the same unit are the same type
- Slow twitch oxidative – slow & fatigue resistant
a. Small amounts of tension, slowly
i. Capable generating tension for long periods of time without running down energy stores
- Single twitch – approx. 2 grams tension
- Approx. 25 ms to generate full tension
- Unfused tetanic force – generates max force after approx. 1 second
ii. Tension can be sustained over long period of time – stays consistent up to an hour
b. Features
i. Large numbers of mitochondria
ii. Small fibres
iii. Well vascularized – myoglobin to facilitate oxygen transfer from blood
- Blood – makes them red; supplies with o2 - Fast oxidative-glycolytic – fast & fatigue resistant
a. Can do both oxidative and glycolytic – o2 or no o2
i. Generate a lot of tension, moderately fast
- Single twitch – approx. 10 grams tension
- Unfused tetanic – takes a few stimulations to reach peak
ii. Somewhat resistant to fatigue – can maintain tension with gradual decrease approx. 15 min
b. Features
i. Moderate # of mitochondria – fewer than slow twitch
ii. Fibres are larger than slow twitch - Fast twitch glycolytic – fast fatigable & only anaerobic
a. White muscle – no o2; does not require o2 to be transported here
i. Generate the most tension
- Single twitch – approx. 50 grams
- Approx. 10 ms to generate full tension
- Unfused tetanic – very few stimulations required to reach peak; faster than others
ii. Fatigue rapidly – can only generate max tension approx. 1 min
b. Features
i. Few mitochondria – breakdown glucose via anaerobic catabolism
ii. Fibres are larger than slow twitch – these are the largest & most tension
Recruitment of motor units
- size of motor units
Slow twitch fatigue resistant – first Motor units recruited; red & oxidative
a. Ex. these will be activated if lifting a light weight
b. Smallest motor neurons
- Each MU has only a few fibres
Fast fatigue resistant – second recruited
a. Motor neurons are slightly larger
Fast twitch glycolytic (fatigable; white muscle) – last recruited
a. Ex. lifting a very heavy weight
b. Largest motor units – most fibres
- Motor unit has many fibres
Size principle – size matters
Homeostatic control mechanisms
Organs that have endocrine functions
Set point range (examples) & integration
Homeostatic control mechanisms – allows coordination between body systems
Many not classically endocrine organs have endocrine functions
Maintain set point range – metabolism, salt and water, reproduction, growth
Requires integration
• Positive input – stimulation
• Negative input – inhibition
Origins of endocrinology
Early 20th century – William Bayliss and Ernest Starling
Identifying cause and effect functions
• Anatomy (form) and physio (function)
Hypothesized control of secretion of alkaline juice from the pancreas into the duodenum – nervous of chemical control?
a. Began with Pavlov’s dog experiment – is there endocrinology associated with it
b. Anatomically
o Stomach goes into duodenum & pancreas opens into duodenum
c. Physio
o The stomach produces acidic chyme – too acidic for duodenum to digest properly
o Pancreas secretes alkaline juices
Experiment
a. Severed neurons that connected pancreas in dogs – found there was still entry of alkaline fluids into duodenum
b. Concluded a blood borne agent
o Stimulus of endocrine agents – promotes pancreas to release endocrine juices & alkaline juices
c. Secretin – later was identified as the hormone that promotes secretion of alkaline fluid from pancreas
Presented these findings in 1905 in the royal college of physicians of London
a. Pharmacopoeias – a legally binding collection of standards and quality specifications for medicines used in a country or region
b. Hormone – Greek for “I excite or arouse”; carried from the organ where they are produced to the organ which they affect by means of the blood stream and the continually recurring physiological needs of the organism must determine their repeated production and orientation through the body
- Released from an endocrine gland into circulation and acts at far site
- This is not entirely true – there are many types of hormones
Variability in hormone effects and production (7)
- tropic vs nontropic
- rhythms
- One endocrine gland can produce many hormones
a. Ex. pituitary gland - The same hormone can be secreted by many tissue types
a. Every cell in the body has the mechanisms to transcribe genes and produce hormones
i. Ex. the brain – not a traditional endocrine gland but has endocrine functions
b. Estrogens and androgens are often sex specific (secreted by sex organs)
i. Also released in other areas – ex. release of estrogen in the brain for neuromodulation - There is more than one target cell for a single hormone
a. Ex. a hormone released to control blood pressure may affect:
i. Endothelial cells of blood vessels
ii. Kidney – controls blood volume
b. Integrates function of different organs - A target cell can be influenced by many hormones
a. Non-tropic hormones – hormones that directly stimulate target cells to induce effects
b. Tropic hormones – act on another endocrine gland to initiate release of other hormones - Secretion varies over time and will be affected by changes in the environment
a. Rhythms – release of hormones is entrained to environmental cycles which vary in interval length and duration
i. Growth hormones – peaks at night
ii. Cortisol – usually peaks in the morning
iii. Melatonin – peaks as night - Hormones can be blood borne or neuronally derived
a. Found in the brain – can regulate neuron function - Hormones can be excreted from tissues that have other functions
Chemical classifications of hormones
- solubility
- type of secretion
- transport
- location
- Peptides – chains of amino acids (3 to 500+)
a. Solubility – hydrophilic
b. Secretion – exocytosis
c. Transport – free active peptide or precursor (inactive form that may be activated via post translational modification)
d. Source – pituitary, pancreas, GI tract etc
i. Occurs everywhere – every cell has mechanisms to secrete proteins - Amino acid derivatives
a. Catecholamines (ex. norepinephrine and epinephrine)
i. Solubility – hydrophilic
ii. Secretion – exocytosis
iii. Transport – 50% to carrier protein
iv. Main source – adrenal medulla
- Not the only site
b. Thyroid hormone (T3 and T4)
i. Solubility – hydrophobic
ii. Secretion – endo & exocytosis
iii. Transport – most bound to carrier
- Hydrophobic relies more heavily on carrier proteins
iv. Source – thyroid gland
- The most specific in terms of cite of synthesis – chemical conditions to synthesize are very harsh
c. Melatonin
i. Solubility – hydrophilic
ii. Secretion – exocytosis
iii. Transport – 50% to carrier protein
iv. Source – pineal gland - Steroids – cholesterol derivatives
a. Solubility – hydrophobic
b. Secretion – diffusion (non polar and small)
c. Transport – most bound to carrier protein
i. Hydrophobic relies more heavily on carrier proteins
d. Source – adrenal cortex and sex steroids
i. Adrenal cortex – cortisol and aldosterone
Synthesis and most translational modification of peptide hormones
examples
- thyrotropin releasing hormone
- adrenocorticotrophic hormone
- Hormone is synthesized via transcription and translation
- Modifications in golgi – may be required in order to become bioactive
a. Undergoes peptide cleavage
b. Addition of functional groups
i. Glycosylation – addition of sugar
ii. Phosphorylation – addition of phosphate group
iii. Sulfation – addition of sulfide group
iv. Amidation – addition of amide group
v. Acetylation – addition of acetyl group
c. Subunit aggregation (ex. insulin receptors)
Examples:
Thyrotropin releasing hormone
- PreproTRH – precursor peptide has 6 copies of 3 AA TRH hormone
a. Must undergo proteolytic activation in order to release the TRH hormone
b. Protein segments in between may be protective – play a role in regulation but understanding of their role is limited - Adrenocorticotrophic hormone – produced in the pituitary
a. Pro-opiomelanocortin – prohormone for ACTH
i. May contain several peptide sequences with biological activity
ii. ACTH – regulates cortisol synthesis and release
secretion of hormones
- negative and positive feedback (and examples)
Feedback control is mainly negative – output counteracts input
a. Common in tropic hormones
- ex. release of TSH (thyroid stimulating hormone) from anterior pituitary -> promotes thyroid hormone synthesis -> releases TH (thyroid hormone) -> TH inhibits production of thyrotropin releasing hormone (TRH) in hypothalamus -> inhibits production of TSH in the pit gland
Can be positive
a. Ovarian cycles
i. Increasing maturation of follicles during ovulation causes increase in estrogen -> estrogen stimulates hypothalamus and causes release of gonadotrophin releasing hormone (GnRH) -> causes further increase in estrogen
b. Letdown reflex in nursing mothers
c. Oxytocin release in contraction of endometrium during birth/patriation
Carrier proteins
- where do hydrophobic vs phillic hormones illicit responses
- dictated by what
Release requires changes in environment – stimulus triggers synthesis and release of hormone
Free hormones bind to proteins and form complexes – very few free hormones within the blood stream
Carrier proteins
1. Often required for both hydrophobic and hydrophilic hormones
a. Hydrophobic – more reliant; more protein complexes than free hormones
o Genomic response – crosses membrane and binds to cytoplasmic or nuclear receptors; leads to transcription of new proteins
- Slow acting – seconds to minutes
b. Hydrophilic – may be bound more loosely
o Highly water soluble – more free hormones than bound
o Nongenomic response – binds to membrane receptors
- Fast acting – minutes to hours
2. Dictated by binding affinity – affinity of hormone to carrier will affect total amount of free hormone in circulation
Types of carriers – can be general or specific to hormone
1. Specific carriers
• Corticosteroid binding globulin (CBG) – carry corticosteroids
• Thyroid hormone binding globulin, thyroid binding globulin, & transthyretin – carry thyroid hormones
2. General carrier
• Albumin – many hydrophilic hormones bind; typically low affinity