Syme Lectures Flashcards
light meromyosin
tail region of myosin heavy chain
heavy meromyosin
neck + head region of myosin heavy chain
trypsin
cuts myosin heavy chain into light meromyosin and heavy meromyosin
papain
splits heavy meromyosin into head (S1) and neck (S2) regions
the head and neck of myosin heavy-chains include:
regulatory (neck) and essential (head) myosin light chains
how many mosyin light chains are present in the myosin heavy-chain complex (2 myosin heavy-chains)?
4
bare zone
0.2 um, segment of thick-filament self-assembly that does not contain heads
one complete spiral of heads in thick filament assembly is:
43nm
each head within a spiral in the thick filament assembly is separated by:
14.3nm
how long is a myosin heavy chain?
150 nm
what do the myosin light chains influence?
ATPase and binding properties of S1 (head region)
what are the two types of contractile proteins?
thick filaments (made from myosin) and thin filaments (made from actin/globular actin/g-actin)
thin filaments
self-assembled from mixtures of multiple g-actins until length reaches 1um
stage 1 (myosin*ATP)
ATP is hydrolzed by ATPase to produce myosinADPPi, in the presence of calcium, forms actomyosinADPPi (a weakly bound crossbridge)
stage 2 (actomyosin*ADP)
release of Pi causes pulling on thin filaments to cause sliding, strongly bound crossbridge, powerstroke
stage 3 (actomyosin)
ADP release, not pulling, stuck in attachment state, rigor state
stage 4
ATP binds and crossbridge separates (myosin*ATP and actin)
if limited sources of calcium:
no contraction, can’t form cross-bridges, relaxed muscle; calcium regulates contraction
if limited sources of ATP:
actomyosin is stuck in rigorstate
diameter and length of a smooth muscle cell
diameter = 2-10um, length=10-500um
attachment plaque
composed of viaculin and alpha-actinin, where thin filaments attach (found in smooth muscle)
dense body
interacts with thin filaments (found in smooth muscle)
what are the two types of smooth muscle?
single unit (visceral) and multi-unit
single unit smooth muscle
found in gut, urinary bladder, and uterus. tissue is made up of many cells but acts as a single unit due to the presence of gap junctions, can spontaneously depolarize (autorhythmic)
myogenic
spontaneous muscle depolarization
what are two examples of autorhythmic muscle contraction?
1) pacemaker potential - membrane potential rises and falls on its own due to a “leaky” membrane
2) slow wave potential - basic electric rhythm, oscillations in ions being pumped, will contract if threshold is reached
multi-unit smooth muscle
cells act independently, not connected by gap junctions, neurogenic (requires nerve excitation to contract), found in iris, focus lens, hair follicles
parasympathetic activation of smooth muscle
cholinergic neurons release ACh to act on muscarinic ACh receptors to cause a second messenger system (IP3 pathway) that causes contraction
sympathetic activation of smooth muscle
adrenergic neurons release norepinephrine or epinephrine which can act on alpha 1 receptors (nor/epinephrine) to produce contraction (via IP3 second messenger pathway) or beta 2 (epinephrine has more potent effect) to produce relaxation
what are the sources of activating calcium for smooth muscle?
1) voltage-activated calcium channels on the cell membrane
2) sarcoplasmic reticulum - membrane bound organelle that stores calcium, not as well developed in smooth muscle but can still regulate contraction
what influences smooth muscle contraction?
concentrations of calcium ions/oxygen/carbon dioxide, pH, nitric oxide NO, serotonin, heat, stretch
myosin light chain kinase (MLCK)
enzyme that can phosphorylate myosin light chains (regulatory mechanism) that enhances cross-bridge formation and thus contraction
how is MLCK activated?
by binding with calcium-calmodulin complex
how is MLCK inhibited?
by phosphorylation (beta 2 receptor activation initiates cAMP second messenger pathway, activated PKA phosphorylates MLCK and inhibits action, reduces contraction)
Rho kinase
activated by serotonin and phosphorylates/inhibits MLC phosphatase, promotes cross-bridge formation, increased smooth muscle contraction
caldesmon
acts on actin filaments to block binding sites for thick filaments, turns off smooth muscle
caldesmon is inactivated by:
- calcium+calmodulin complex
- PKC phosphorylation reduces binding affinity for actin
diameter and length of a skeletal muscle cell
diameter = 5-100um, length = 1 - many cm
myoblast
progenitor cell that can differentiate
when myoblasts congregate, they form a:
myotube
when myoblasts fuse, they form an:
adult myocyte/muscle fibre/muscle cell
myofibril
consists of sarcomeres stacked in series, responsible for the striated appearance/banding pattern of skeletal muscle
sarcomere
functional unit of contraction
Z lines/disk
composed of alpha-actinin, border of sarcomere, where thin filaments attach
A-band
dark band down centre of sarcomere, consists of the entire length of the thick filament, includes sections of overlap with thin filaments
M-line
in the centre of the A-band, anchors the thick filament
I-band
contains light bands/thin filaments only
H-zone
a little lighter than rest of A-band, contains segments of thick filament only
titin
has the ability to generate force, interacts with both myosin and actin
how are thick and thin filaments arranged in skeletal muscle?
in sarcomeres, thick filaments are surrounded by a hexagon of thick filaments in a 2 (thin) : 1 (thick) ratio
what are the two regulatory proteins in skeletal muscle?
1) troponin - spaced along thin filament every 40nm
2) tropomyosin - runs along the thin filament
what did Andrew Huxley discover?
when a muscle shortens, the A-bands don’t change length, but the I-band and the H-zone get shorter
what did Hugh Huxley discover?
neither the thick nor the thin filaments change length
sliding filament theory of muscle contraction
H-zone and I-band length changes during muscle contraction
the number of cross-bridges formed are directly proportional to:
the amount of force generated and the amount of overlap between actin and myosin
what does the troponin complex contain?
troponin T, troponin C - binds calcium, troponin I, all bound onto tropomyosin which covers the myosin binding site on actin
when calcium binds to troponin C…
troponin I releases actin and myosin binding site on thin filament is exposed (allows cross-bridge formation)
excitation-contraction coupling (ECC)
depolarization of muscle cell by sodium influx following AChR binding causes action potential propagation along the muscle cell, coupling of depolarization to release calcium from the SAR is accomplished through the dihydropyridine receptor and ryanodine receptor
terminal cisternae
swelling of sarcoplasmic reticulum near T-tubules
triad
3 adjacent membrane-bound components, terminal cisternae of two sarcoplasmic reticulum units + t-tubule
transverse tubules (T-tubules)
invaginations of the membrane, most mammals also have voltage-gated sodium channels on T-tubule membranes
dihydropyridine receptor
voltage gated calcium channel in most cells. in muscle cells (found on T-tubule membrane), activation results in opening of ryanodine receptor pore (on sarcoplasmic reticulum membrane, increases free intracellular calcium levels for muscle contraction)
sarcoendoplasmic reticulum calcium ATPase
uses active energy to pump calcium out of the cytoplasm into the sarcoplasmic reticulum
“Plunger Model”
1) ACh binds nicotinic receptors on muscle
2) sodium influx
3) action potential
4) activation of dihydropyridine receptors
5) opening of ryanodine receptors
6) calcium ions diffuses out of sarcoplasmic reticulum
(when membrane depolarizes, DHPr unplugs RyaR
calsequestrin and parvalbumin
calcium binding proteins in sarcoplasmic reticulum, decreases free calcium, lowers concentration gradient of free calcium for calcium ATPase to work more easily (release free calcium when free calcium concentration drops in SR, being pumped out of cell)
latency
delay between action potential and force generation
contractile element (CE)
sarcomere (organized in series in a myofibril)
series elastic element (SE)
stretchy things in series to CE, modulates force contributed by CE, force is transmitted directly through them, also counts if it’s outside of the muscle cell
parallel elastic element (PE)
parallel elasticity to CE, contributes to force of contraction
active force=
CE + SE (force produced by CE and experienced by SE)
total force produced by muscle=
CE + PE
isometric contraction
muscle length does not change: in response to changes in muscle force, CE and SE change in equal and opposite directions
isotonic contraction
force of muscle contraction is constant, length of muscle cell changes (SE does not change but CE changes length)
twitch
response to a single action potential, all-or-none
twitch summation / temporal summation
continuous pulses before muscle returns to baseline force, causes tetanus
fused tetanus
the highest possible force, muscle is saturated with calcium, no oscillations
motor unit recruitment
controlling the number of muscle cells that are activated
what is integration and where does it occur?
integration determines firing of alpha motor neurons and thus determines muscle contraction, it occurs at the ventral horn in the spinal cord
final common pathway=
alpha motor neuron (can connect/synapse with multiple muscle cells, if action potential is fired, all muscle cells contract and act as a single unit)
motor unit
alpha motor neuron and all the muscle cells it synapses with
spatial summation
each muscle can have multiple motor units that each belong to a separate alpha motor neuron, summation occurs if many motor neurons (and muscle cells) are activated in space (increases force of contraction)
what factors can affect force of muscle contraction (and are not usually used specifically for the purpose of force modulation)?
- length-tension relationship: filament overlap
- length of filament (longer length=more crossbridges)
- more sarcomeres working in parallel
- adding more muscle fibres (cells) working in parallel = more sarcomeres working in parallel
- damage to myofibre = muscle hypertrophy by formation of more myofibres
speed of muscle shortening =
(speed of 1/2 sarcomere * 2) * # of sarcomeres in series
lower velocity of shortening=
lower force of contraction
the force-velocity relationship can be described by a:
Hill Curve, rectangular hyperbola, curve does not form asymptote inside the axis, inverse relationship between velocity of shortening and force
maximum velocity of shortening
fastest that a muscle can go, F = 0, muscle can only contract, cannot have negative force
as velocity of shortening increases:
fewer attached cross-bridges, average force of cross-bridges decreases
work performed by muscle contraction =
force * distance it shortens
power of muscle contraction =
rate of doing work = J/s = N*v (force * velocity)
when is power at a max?
at 20-40% of Vmax
when is power = 0?
when force is very high (v = 0) and when velocity is very high (Vmax)
what is the energetics of muscle contraction?
75% heat, 25% work
what is the typical muscle efficiency?
25% (W out/E in)
what is the efficiency of isometric contractions?
0 (no work because no change in length)
what are sources of ATP for muscle contraction?
1) glycolysis (anaerobic)
2) oxidative phosphorylation (aerobic)
3) creatine phosphate + ADP to create ATP and creatine
what are five ways you can classify muscle fibres?
1) fast vs. slow
2) anaerobic vs. oxidative
3) fatiguable vs. fatigue resistant
4) twitch vs. tonic
5) myosin heavy chain (MHC) type
tonic muscle fibre
don’t normally fire action potential, membrane depolarization produces graded potentials, in mammals found in muscle spindles and extraocular muscles
multiterminal innervation
one motor neuron has many branches onto a muscle cell
what are four types of vertebrate twitch muscle fibres?
1) slow twitch (type I MHC)
2) fast twitch oxidative/glycolytic (FOG) (type IIa MHC) - rapid, repetitive movements
3) fast twitch glycolytic (FG) (type IIb MHC) - not present in humans
4) type IIx MHC - intermediate properties between IIa and IIb, fastest type II fibre in humans
how do fast-twitch fibres compare to slow-twitch fibres in force vs velocity and power?
fast-twitch fibres produce about the same force of contraction but can contract faster and produce greater power at higher velocities
alpha motor neurons with large cell bodies tend to innervate:
fast muscle fibres, large cell bodies = more excitation to reach threshold for action potential
alpha motor neurons with small cell bodies tend to innervate:
slow muscle fibres, small cell bodies = activated faster
Henneman’s size principle
relationship between size of cell body and type of muscle (slow/fast)
spinal reflexes/simple reflexes
hard-wired, does not involve learning
monosynaptic reflex
afferent + efferent alpha motor neuron
polysynaptic reflex
afferent + efferent alpha motor neuron + interneurons (several)
reciprocal inhibition
one synapse excites and the other inhibits, ex. pain/withdrawal reflex activates one muscle to withdraw from painful stimulus with inhibiting antagonist muscle
