Physiology Week 9 (Lecture 1)

skeletal muscle vs neurons electrical signals

skeletal muscle: uses electrical signals to trigger contraction & generate force

• graded potentials: vary in magnitude

• action potentials: all-or-none signals, info encoded by frequency

neurons: use electrical signals to communicate

skeletal muscle vs neurons Ca²+ release

skeletal muscle: Ca²+ triggers contraction/force generation

neurons: Ca²+ helps trigger neurotransmitter release

skeletal muscle functions

1. movement of bones

2. maintain posture & body position

3. stabilize joints (bring back to original state after disturbance)

4. head generation (shivering)

• muscle generated heat because ATP use is inefficient

  • large portion of energy consumed is released as heat rather than converted into mechanical work

skeletal muscle organ vs. muscle cell

muscle organ: muscle cells, connective tissue, blood vessels, & nerves

muscle cell: individual cell that generates tension by contraction

• single skeletal muscle cell: muscle fiber/myocyte

connective tissue organization: endomysium

• surrounds each individual muscle fiber (muscle cell)

• relatively loose, flexible connective tissue

• supports cell while allowing its shape to change during contraction

connective tissue organization: perimysium

• surrounds a bundle of muscle fibers called a fascicle

• provides a stronger support around the bundle

connective tissue organization: epimysium

• surrounds entire muscle organ

• made of dense irregular connective tissue

• connects w/ dense regular connective tissue of tendons

order muscle fibers to bone

muscle fibers

connective tissue layer (endomysium, perimysium, epimysium)

tendon: strong, dense regular CT that transfers muscle force to bone

periosteum: dense CT covering outer surface of bone

bone

compartment syndrome

epimysium & other surrounding connective tissues limit how much the muscle compartment can expand

• if pressure in compartment rises too much, blood flow can be reduced & nerves can be compressed

• similar to principle of swelling-related pressure problems in brain

skeletal muscle cells size & nuclei

single skeletal muscle cell: muscle fiber/myocyte

• large cells: 10-100 um, some fibers can be a foot long

  • contain large amounts of protein & require a lot of energy to function

multiple nuclei

• 30-100 nuclei per millimeter of muscle fiber

• a very long fiber can contain 1000s of nuclei

• nuclei are distributed throughout the cell (spread out)

how skeletal muscle fibers form

through fusion of developing muscle cells

• in mature muscle, satellite cells are muscle stem cells that help with repair & growth by contributing to muscle tissue

  • allows a large cell to maintain & produce proteins

muscle cell vocab words

plasma membrane sarcolemma

cytoplasm sarcoplasm
smooth endoplasmic reticulum sarcoplasmic reticulum

muscle cell myocyte/muscle fiber

bundles of contractile filaments in cell myofibrils

action potentials

action potentials: stick to plasma membrane of axons, axon terminal, axon hillock

• used on surface of skeletal muscle cells

• needed to trigger Ca²+ release (transverse tubules extend into cell for this)

muscle fiber composition

mitochondria: produce ATP

glycogen: stored carbs that can be broken down into glucose

• glycosomes are clusters of glycogen & not membrane bound

myoglobin: stores O2 inside muscle cells

• has 1 protein chain, 1 heme group, can bind 1 O2 molecule

myofibrils: structures made of organized actin/myosin that generate tension

• actin & myosin

sarcoplasmic reticulum: stores Ca²+ for muscle contraction, surrounds myofibrils

muscle fibers are large…

electrical signal at its surface must reach deep inside the cell to coordinate contraction

T-tubules (transverse tubules)

inward extensions of the sarcolemma

• surrounded by the sarcoplasmic reticulum

• carry electrical signals from the surface toward the interior of the muscle fiber

• their interior remains continuous with the extracellular fluid

sarcoplasmic reticulum

specialized form of smooth endoplasmic reticulum

• stores Ca²+

• releases Ca²+ when muscle fiber receives appropriate signal

• takes Ca²+ back up after contraction so muscle can relax

triad

allows T-tubule to trigger Ca²+ release from sarcoplasmic reticulum

• 1 tubule in the middle (communicates electrically to sarcoplasmic reticulum)

• 1 enlarged region of sarcoplasmic reticulum on each side of tubule

neuromuscular junction

synapse between a somatic motor neuron & a skeletal muscle fiber

function: turn a nerve signal into an electrical signal in the muscle

steps occurring at the neuromuscular junction

1. Motor Neuron Action Potential Arrives

• the electrical signal reaches the nerve terminal

2. Ca²+ Enters the Nerve Terminal

• voltage gated Ca²+ channels open, triggering neurotransmitter release

3. Acetylcholine is Released

• vesicles release AcH into synaptic cleft via exocytosis

4. Acetylcholine Binds Nicotinic Acetylcholine Receptors

• these receptors are located in the muscle’s motor end plate

5. The Muscle Membrane Depolarizes

• the receptor channel allows both Na+ & K+ to move, but net effect is positive charge entering the cell

6. Muscle Action Potential Begins

• if threshold is reached, voltage gated Na+ channels generate action potential that spreads along sarcolemma & into T-tubules

end plate potential

local, graded depolarization caused by acetylcholine binding to its receptors

muscle action potential:

• all-or-none electrical signal that spreads along the muscle membrane

• the motor neuron connects to a relatively small region of the muscle fiber, but the muscle action potential spreads far beyond that small region

nicotinic acetylcholine receptors

ionotropic receptors: receptor is an ion channel…lets ions through

• 2 acetylcholine bind to receptor & open channel

• net movement of positive charge into the muscle depolarizes its membrane

signal stopped by:

• cholinesterase: breaks down acetylcholine in the synaptic cleft

  • stops stimulation of receptor

skeletal muscle vs. cardiac & smooth muscle receiving inputs

skeletal muscle: receives excitatory signal at neuromuscular junction

• when stimulation ends & Ca²+ is removed from the sarcoplasm, muscle relaxes

cardiac & smooth muscle: can have both excitatory/inhibitory regulatory inputs

blockage of channels

block voltage gated Na+ channel:

• can’t get muscle to contract

• inhibits depolarization

block voltage gated K+ channel:

• causes hyperexcitability

block voltage gated Ca²+ channel:

• no exocytosis…can’t get muscle to contract

• prevent exocytosis

toxin

Na+ channel blockade:

• tetrodotoxin-blocks signaling to muscles in the mouth

• lidocaine-reduces nerve signaling, including pain signals

• novocaine-reduces nerve signaling, including pain signals, dampens action potentials to brain

K+ channel blockade: hyperexcitability of sensory neurons, depolarization, muscle twitching

• charybdotoxin

• iberiotoxin

• apamin

Ca²+ channel blockade:

• w-conotoxin-prevents neurotransmitter release (acetylcholine)

botulinum toxin

interferes with SNARE proteins needed for synaptic vesicles to fuse w/ membrane

• without fusion…acetylcholine can’t release normally

• reduces muscle activation

• need anaerobic conditions

botox (fixes muscle disorders/migraines)

botulism (comes from honey, infant can’t dilute out toxin)

tetanus toxin

interferes with neurotransmitter release, affects inhibitory neurons

normally, inhibitory neurons help restrain motor-neuron activity

when inhibition is lost, motor neurons can become excessively active, causing rigidity & spasms

botulinum toxin & tetanus toxin

botulinum toxin:

• lowers acetylcholine release at neuromuscular junction

• reduced muscle activity

tetanus toxin:

• lowers inhibitory signals to motor neurone

• excessive muscle activation

curare-like compounds

block nicotinic acetylcholine receptors

even if acetylcholine is released, muscle can’t respond normally

severe effects can impair breathing because respiratory muscles can’t contract properly

acetylcholinesterase inhibitors

prevent normal acetylcholine breakdown

• continues stimulating receptors

muscles can’t relax

muscle contraction can be interrupted by

blocking the action potential

Ca²+ dependent acetylcholine release

acetylcholine receptors

acetylcholine breakdown

muscle action potentials (steps)

after end plate potential reaches threshold, muscle fiber generates an action potential

1. resting membrane potential

2. depolarization (voltage-gated Na+ channels open, Na+ influx)

3. repolarization (Na+ channels inactivate & K+ channels open…K+ efflux)

4. recovery (Na+ channels return to their available state, membrane goes back to resting potential)

absolute/relative refractory periods limit how soon next action potential occurs

more K+ channels open in

resting muscle cell

• during resting membrane potential…moves closer to K+ equilibrium potential

Ca²+ & force

intracellular Ca²+ rises…muscle force increases

when Ca²+ is removed from sarcoplasm & returned to sarcoplasmic reticulum…force decreases & muscle relaxes

more cytosolic Ca²+……more force

muscle action potential only lasts a few milliseconds

• resulting contraction lasts much longer…100s of milliseconds

  • because: Ca²+ release, Ca²+ movement through sarcoplasm & Ca²+ removal takes time

nicotinic acetylcholine receptors & muscle relaxation

nicotinic acetylcholine receptor at the skeletal muscle motor end plate is an ionotropic receptor

• has 5 subunits

• require 2 acetylcholine to bind/activate

ligand-gated ion channel

2 acetylcholine binds to receptor

channel opens & allows cations Na+/K+ to move

because Na+ entry predominates, membrane depolarizes

how does the muscle stop contracting?

cholinesterase: breaks down acetylcholine in synaptic cleft, stopping stimulation of the motor end plate

muscle relaxes & cytosolic Ca²+ decreases

skeletal muscle vs. cardiac & smooth muscle neuron input

skeletal muscle: neuron input at the neuromuscular junction is excitatory

• when stimulation stops, muscle can relax

cardiac & smooth muscle: their activity can be regulated by inhibitory & excitatory inputs, depending on the receptor & tissue

excitation-contraction coupling

this process links a muscles action potential to the contraction machinery

step by step:

1. muscle action potential spreads along sarcolemma

2. action potential travels down the T-tubules

3. voltage-sensitive proteins called dihydropyridine receptors detect change in membrane voltage

4. in skeletal muscle, DHPRs are mechanically coupled to ryanodine receptors in sarcoplasmic reticulum

5. activation of DHPRs causes ryanodine receptors to open

6. Ca²+ is released from the sarcoplasmic reticulum into the sarcoplasm

7. Ca²+ enables actin & myosin to interact and generate force

Neuron vs. skeletal muscle Ca²+ enters and releases

neuron: Ca²+ enters from extracellular fluid at the nerve terminal to trigger neurotransmitter exocytosis

skeletal muscle: Ca²+ is released primarily from the sarcoplasmic reticulum, an intracellular store, to trigger contraction

myofibrils & organization of contractile proteins

myofibrils:

• actin: forms thin filaments

• myosin: forms thick filaments

skeletal muscle fibers-1 muscle cell

myofibrils-bundles of contractile filaments

sarcomeres-repeating functional units

actin/myosin filaments-generate tension

sarcomere

functional unit of contraction in skeletal muscle

extends from 1 z-disc to the next z-disc

z-disc: mark the ends of a sarcomere & anchor thin filaments (actin)

A-band “dark”

the full length of the thick myosin filaments, including areas where actin overlaps

I-band “light”

thin actin filaments without overlapping thick myosin filaments

H-zone

the central region of the A-band containing myosin without actin overlap

M-line

the center of the sarcomere, where myosin are organized

Z-disc

marks the boundary of each sarcomere & anchors actin

strucutres

A-band: myosin & actin

I-band: in between myosin, only actin

H-zone: myosin only in center

Z-disc: end of sarcomere, anchors actin in place

myofibril/myofilaments

myofibril: bundle of acting/myosin

myofilaments: actin or myosin

titin

large, elastic protein

connects the thick filament (myosin) region toward the z-disc

keeps myosin properly positioned

helps sarcomere resist excessive stretching