neuro establishing membrane Flashcards
b. A + B–> E –>AB
cell needs to have the right substrates and molecules in order to perform this reaction
all about protein synthesis and the role of the membrane
cellular physiology begins with access to the internal environment when a cell is
Selective permeable
at the membrane
describe membrane structure
i. Phospholipid bilayer oriented so heads are exterior and interior surfaces of the membrane; tail groups are directed inward towards the center of the membrane
hydrophobic inner
Fluid Mosaic Model)
describe membrane proteins that are relatively free to float around in the membrane and they can concentrate in certain areas of the membrane if needed
types of movements allows by phospholipid bilayer
simple and facilitated (you need a transport molecule to bind)
diffusion can be facilitated
this is how glucose moves
b. Factors that affect diffusion and diffusion rate:
i. Permeability (P) of the membrane
ii. Area: D = PxA
iii. Concentration Difference D(Co-Ci)
diffusion as it relates to permeability and area
a. Diffusion = permeability x area
size of a gradient also impacts net diffusion
V. When does movement of substances across selectively membrane stop?
Diffusion proceeds to equilibrium, NOT equal concentrations
If only one substance and no concentration gradient, then your net diffusion will be 0 but usually other forces and molecules in play
An _________ can make charged particles move in the absence of a concentration gradient
An electric potential can make charged particles move in the absence of a concentration gradient
VI. Nernst Potential
Find the equilibrium point for an ion in solution when there is a semipermeable membrane that is permeable to that ion
equilibrium potential
should be able to apply a positive charge that would counteract diffusion or concentration gradient
allows us to figure out the electrical current at which point the system would be in equilibrium
Nerst equation only works with what types of ions
univalent
so not Ca (2+)
osmotic pressure is created with
non diffusible elements on either side of the membrane
osmole is
the molar content of non diffusible elements
what is needed to phosphorylate enzymes
i. Need ATP to phosphorylate enzymes
In nerve and muscle physiology, this is important for establishing the concentration gradient that we need to use to create that electric voltage we need across the membrane
Na/K pump
functions of Na/K pump
Helps maintain osmotic balance
Electrogenic (separates charge unevenly and creates potential for electrical current)
step 1 of Na/k pump
- takes in 3 Na molecules, which are bound to the protein.
step 2 of Na/k pump
ATP phosphorylates alpha subunit, stimulating conformational change
step 3 of Na/k pump after ATP phosphorylates alpha subunit, stimulating conformational change
Pump open to outside, ready to start second half of cycle
step 4 of Na/k pump after
Pump open to outside, ready to start second half of cycle
2 K accepted from outside
step 5 of Na/k pump after
2 K accepted from outside
dephosphorylation stimulates conformational change
step6 of Na/k pump after . dephosphorylation stimulates conformational change
- 2 K expelled to inside; pump returns to initial state
Na/k pump helps establish what charge
So moving 3 Na+ out, and 2 K+ in =net positive charge outside and net negative charge inside
this is a membrane phenomenon
remember sodium concentrations 134-145
whereas K 3.5-5
Active Transport Mechanisms: Secondary
spend ATP to set up gradient that allows us to move molecules in the same or opposite directions
imbalance of charge is a form of
“potential” energy
relative difference of electrical charge between the two sides of the membrane
diagram of pulling back the bow from the arrow
forces at play with a cell and how they relate to NERST
membrane is relatively permeable to potassium
Na/k creates high intracellular K
flux of K ions would want to move out but
electrostatic pressure: outside is more positive and this is a repelling force that keeps
as the ion is fluxing the concentration gradient is reducing diffusion pressure
NERST looks at the balances of these and looks at where you can apply an electrical current to stop the flow of ions even if the concentration is not equal
EMF =
electro
motor force
voltage that you have to apply to prevent the movement of ions
C1/C2
concentration inside and outside of the cell
Factors effecting diffusion potential
Polarity of each ion involved is important
Permeability of membrane for each ion
Concentration difference of each ion across membrane
Modified Nernst for multiple ions
: Goldman-Hodgkin-Katz equation
Calculates the membrane potential at rest given the different concentration gradients
GHK equation accounts for
Considers concentration differences of the ions most responsible for the membrane potential
Considers permeability because ions can only contribute to membrane potential if the membrane allows it/if they can diffuse
chloride and it’s negative charge is accounted for
GHK tells us
can us it to calculate the membrane potential at rest given the different concentration gradients
ions can only contribute to membrane potential if the membrane allows it/if they can _______
ions can only contribute to membrane potential if the membrane allows it/if they can diffuse
b. Voltage across membrane referred to as __________
b. Voltage across membrane referred to as “membrane potential”
c. In nerve cells, typically the membrane potential is
c. In nerve cells, typically -60- -90mV
Inside of the cell is more negative than the outside
remember the picture of the capacitor this is how the membrane acts
Factors influencing membrane potential
a. Activity of the Na/K pump
b. Membrane leak/Permeability
c. Effect of leak on membrane potential can be inferred from Nernst potential for each ion involved
d. Hyperpolarization by ATPase
If membrane only leaky to 1 of the ions, then that ion is going to….
If membrane only leaky to 1 of the ions, then that ion is going to move the membrane potential towards its own reversal potential
is i make the membrane permeable it will move the concentration toward equilibrium and it’s own reversal potential
can use the NERST to calculate where the potential would go in this case
membrane gets re-polarized by the
i. Gets repolarized by the ATPase
a. Vk
nerst potential/reversal potential for K is pretty negative
Vna
membrane potential is very positive; if open channels for Na, then it’s going to rush in to the cell
what this tells you is that Na is oging to rush into the cell
Vm
membrane potential is close to K’s reversal potential b/c of the leakiness to K, tending to keep the membrane near its own reversal potential
describe AP
When some threshold is reached, massive opening of Na channels and the membrane potential is driven towards the reversal potential for Na which is positive so you have the upstroke
when the membrane potential is drive back down this is an example of what physiological process
then slower K channels open and the membrane potential is driven back downward towards resting potential (downstroke)
skeletal m accounts for what %
a. 40% of the body
i. Move our skeleton
skeletal muscles are specialized only to
b. Can only contract
Muscle can either extend or flex a joint (it can’t do both)
Individual cells contain contractile protein calles
Individual cells contain myofibrils
myofibirls are bundled together as fibers and fasciclesc
skeletal muscle is arranged in big bundles called and little bundles called
a. Bundles (fascicles) of bundles (fibers)
Myofibrils bundled together as ___ and these are bundled together as_____
i. Myofibrils bundled together as fibers. Fibers bundled together as fascicles
this surrounds muscle cell
c. Sarcolemma surrounds muscle cell
Myofibrils are contractile elements containing _______
d. Myofibrils are contractile elements containing myofilaments
Mitochondria what % of skeletal muscle
e. Mitochondria (2% in skeletal)
this stores calcium
f. Sarcoplasmic reticulum stores calcium
______lines the surfaces of the fascicles
- Epimysium lines the surfaces of the fascicles
myofilaments
actin (thin)
myosin (thick)
a small purple protein which coil around the coil of actin protein
i. Tropomyosin
sit attached both to actin and tropomyosin molecules
ii. Troponin
describe the arrangement of actin
helical coil of actin subunits. Actin arranged in long polymers, 2 long polymers are coiled around each other with a particular frequency
describe the arrangement of myosin
Myosin has head groups w/ 2 hinges (one hinge at the attachment of the head group and one lower down near the tail region)
skeletal muscle contraction always begins with
a. Begins with stimulation by nervous system in skeletal muscle
Motor unit
Individual motor nerve fibers and all of the muscle fibers that are innervated by that nerve
if you have a muscle with a lot of smaller motor units you have a lot more options
larger muscles have what type of motor untis
ii. Larger muscles that move the limbs have big motor units - you don’t require fine movement with the limbs
1. Each individual neuron can stimulate a lot more individual muscle fibers. So motor units are fewer but bigger
smaller muscles have what type of motor units
iii. Smaller muscles have small but numerous motor units - required for dexterity
contents at NMJ of skeletal muscle
iv. The contents here at the NMJ is Ach, it diffuses across the space. Across the gap Ach will bind to a receptor on the postsynaptic membrane/motor end plate
takes two Ach to open the channel
what type of ion channel controls AP of skeletal muscle
This is ligand gated channel and it is a positive ion channel
it will allow Na to flux into the cell and drive the membrane potential towards Na’s reversal potential = Action potential
what type of ion flux mediates the release of Ach in the NMJ
When electrical charge comes down the membrane, you see a Ca++ flux that mediates the movement of vesicles to the
Sarcoplasmic reticulum releases its store of ______ under the influces of
releases store of Ca under the influence of …?
b. Union between nervous and muscular systems
NMJ
uses AcH AS nt AND BINDING RECEPTOR usually triggers an AP and causes release of Ca from sarcoplasm
Protein heads of myosin are known as the____ and they extend away from the body of the filament
Protein heads of myosin are known as the cross bridges and they extend away from the body of the filament
Myosin, each molecule is composed of 6 polypeptide chains
i. Head region and a tail region
Actin (thin) filaments made of 2
helically coiled ______
these strands are made up of _____ which is attached to one ADP
Actin (thin) filaments made of 2 helically coiled F-actin strands
F-actin strands made of G-actin which is attached to one ADP
when in contraction actin filaments are closer to the center of the the
Contracted state where actin filaments are closer to the center of the sarcomere where they are drawn that way by the thick filaments
Troponin made of 3 protein subunits
name them and what they bind to
i. TI binds actin
ii. TT binds tropomyosin
iii. TC binds calcium
Ca is where waiting to be released under what condition
Ca is in the SR waiting to be released when a muscle undergoes an action potential)
how does troponin tropomyosin complexes work
Troponin/tropomyosin complexes inhibit binding of cross bridges by physically blocking binding sites that the myosin head groups want to attach to when the muscle is at rest
k. When AP comes down the membrane of the muscle cell, the voltage gated Ca channels release the store of Ca.
Ca binds to its binding site on the Troponin complex (TC subunit)
this will release the myosin heads so they can bend and pull the ends of the sarcomere togehter
role of ATP in muscle contraction
ATP binds to the head of the myosin cross bridge and it is hydrolyzed and causes myosin head group to reset to its open posture
i. Open head group has the separated ADP and Pi (hydrolyzed pieces of the ATP still attached)
this is stored energy from the hydrolyses of ADP
when is the myosin head at thigh energy configuration
when the aDP and P (hydrolyzed aDP) are attached to the head group and reset to an open posture
here it can attach and close and a new ADP will take the place
Increasing tension developed with stretch (maximum at approx. 110% of normal sarcomere width)
is characteristic of single or whole m fibers
single
Tension limited by the ends of the myosin filaments
If you go beyond the 110% you lose the amount of tension you can develop
Shortening sarcomeres does what to tension
limits tension as z-lines contact myosin filaments
energy required for contraction
a. ATP required in large amounts
b. Muscle sequester short supply
c. ADP must be phosphorylated and returned to high energy ATP state to keep the muscle moving
how do we phosphorylate ADP
a. Creatine phosphate
b. Glycogen:
c. Creatine Synthesis
i. Can phosphorylate very quickly but can’t keep up for very long
ii. Tends to be the first thing we draw on when we contract muscle
a. Creatine phosphate (phosphocreatine) stored in muscle provides, fast but short-lived source of phosphate. Stored in levels about 5x greater than raw ATP
when do we utilize glycogen for muscle contraction
glycogen takes longer but will mobilize and take over for creatine phosphate
The Mother Lode of ATP
a. Oxidative phosphorylation:
dietary sugars broken down first through glycolysis and the Krebs cycle then combine with oxygen as part of an enzymatic cascade producing ATP in large numbers as a by-product
c. Creatine Synthesis
- Comes from arginine in the kidneys then goes through a few steps in the liver to form creatine. Creatine is phosphorylated by creatine phosphate into creatine phosphate which can give off the phosphate molecule to phosphorylate ADP
compare ATP pathways
greatest to lowest
a. CP: 4M/min ATP produced by phosphorylation through creatine phosphate but it lasts only for seconds
b. Glycogen/lactic acid (anaerobic): 2.5M/min for minutes
i. Glycogen pathway is anaerobic and it leads to lactic acid production
c. Oxidative phosphorylation: 1M/min of ATP as long as the food holds out!
i. You can do this forever as long as there is fuel in the machine
Isometric relates to what development of tension
“same length.” Tension = Load
generate tension without shortening the lengt
isotonic contraction
Tension > load
i. Muscle tone remains the same throughout, tension is greater than the load
ii. Ex - when you pick something up
smooth contraction when you pick something up is isotonic
isometric
or lengthening
c. Isotonic = Tension > load
Muscle tone remains the same throughout, tension is greater than the load
- if you try to pick up something you can’t hold
you will have what type of contraction
d. Lengthening contraction = Tension < Load
ii. Muscle starts to lengthen under the load but it still develops tension
but still develops tension
large fibers, very strong fibers
a. Fast Fibers
Large SR = large, fast ion release. Large supply of glycolytic enzymes.
oxidative metabolism with fast fibers
Oxidative metabolism less important, blood supply reduced, fewer mitochondria. Fatigue quickly.
i. Can generate a great deal of strength quickly but fatigue quickly
smaller, more extensive blood supply, increased mitochondria, large myoglobin content, slow fatiguing.
small fibers
small fibers fatigue how compared to fast
more slowly but they generate mroe tension
changing contraction by summing motor unit activity over time and its done by altering the frequency of stimulating APs
XVIII. Temporal Summation
changing contraction by summing motor unit activity over time and its done by altering the frequency of stimulating APs
XVIII. Temporal Summation
recruitment of muscle fibers
i. Smaller motor units contract first, but with growth of signal strength, larger motor units are recruited (smaller motor neurons are more excitable)
1. Larger motor units need a bigger signal to contract
2. Nerves for small motor units are generating AP first
a. At some level contractions fuse into state of sustained contraction referred to as ______
a. At some level contractions fuse into state of sustained contraction referred to as “tetanus.”
b. Nearly every movement involves tetany
staircase effect of muscle contraction
b. Step like increase in strength of contraction after period of rest (staircase effect). May occur due to flooding of the sarcoplasm with calcium
i. Period of rest gives SR to accumulate more Ca so it releases more Ca next time it is stimulated
smooth tension with contraction is maintained by
we alternate motor untits
what is muscle tone
a. Resting tension on the muscle
Results from low baseline rate of nerve impulses from the spinal cord causing low level of release of NT which sets muscle tone and provides trophic effect which provides bulk of your musculature
fatigue increases in proportion to the loss of
a. Increases in proportion to the loss of glycogen stores
b. Transmission of nerve impulses at the NMJ also reduced after prolonged stimulation due to inability to keep up with the recycling of the NT
muscle must cross what?
a. Muscles apply tension at insertion points on bone
b. Work with joints to affect movement of the skeleton
i. Muscle must cross a joint
how does muscle tension work as a lever system
Force related to the distance of the attachment from the fulcrum, the length of the lever arm to be moved and the original position of the lever.
The finger representing the attachment point and at a great distance from the lever in order to be able to lift the mass. We can’t do that in our body.
how is bicep strength limited
Our biceps is not attached at a great distance from the elbow so it limits the strength that can be generated. If it was attached at the wrist, that would allow for a lot more strength
how do muscles change
fibers?
sarcomeres?
a. Almost continuous process
b. Fiber number changes rare
c. Fiber hypertrophy by addition of myofibrils
i. When you exercise, your muscle gets bigger
d. New sarcomeres added with stretch
e. Increase in metabolic enzyme and glycogen storage, blood supply with sustained aerobic activity
why do we have atrophy with the loss of innervation
when you lose innervation of the muscle, you lose the trophic effect of the constant low level of NT that is released so
what happens when we have de-innervation of a muscle
b. Most fibers destroyed and replaced by fibrous or fatty tissues
what are macromotor units
how do thye compare to original muscle
a. Neighboring motor units can sprout new branches to re-innervate muscle fibers resulting in “macromotor units.”
i. Macromotor units have less dexterity than the original muscle but they do preserve some fxn
Duchenne MD
a. Heritable absence of dystrophin (protein required for muscle structure)
b. Males, females have 50% chance of carrying/passing mutation
c. Onset of progressive weakness leading to paralysis at 3-5 yr, most lose ability to walk by 12 yo
d. Becker MD similar but less severe disorder of dysfunctional dystrophin
Adult MD
a. Fascioscapulohumeral MD - slowly progressive disorder of face, arms, shoulder beginning in teens
b. Myotonic - MC adult form characterized by cardiac abnormalities and cataracts, swan neck, drooping eyelids
MD
a. Mostly affects boys (rarely girls).
b. Often brothers or male relatives have same problem.
c. First signs appear around ages 3 to 5: the child may seem awkward or clumsy, or he begins to walk ‘tiptoe’ because he cannot put his feet flat. Runs strangely. Falls often.
d. Problem gets steadily worse over the next several years.
e. Muscle weakness first affects feet, fronts of thighs, hips, belly, shoulders, and elbows. Later, it affects hands, face, and neck muscles. “Walk up” from seated/lying position.
f. Most children become unable to walk by age 10.
g. May develop a severe curve of the spine.
h. Heart and breathing muscles also get weak. Child usually dies before age 20 from heart failure or pneumonia.
