Membrane Physiology, Nerve, and Muscle Flashcards
Fick’s law of diffusion states that flux is proportional to?
(Surface area x Concentration difference) / Membrane Thickness
Three factors affecting rate of diffusion and how?
Concentration difference - proportional to rate accdg to fick law
Potential difference - electric forces
Pressure difference - higher pressure means faster diffusion
Define osmotic presssure
Amount of pressure required to stop osmosis
What is an osmole?
1 gram molecular weight of osmotically active substance
Osmolality vs osmolarity?
Osmolality - osmoles per kg water
Osmolarity - osmoles per liter solution
Osmolality determines osmotic presure, osmolarity is easier measured
Calcium channel and sodium channels play a role in depolarizing phase of the action potential. How to they differ?
Calcium - slow channel, sustained depolarization
Sodium - fast channel, initiation of action potential
Opening of the fast channels in cardiac muscle cause what?
Spike portion of action potenntial
Opening of the slow channels in cardiac muscle cause what?
Plateau of action potential - sustains contraction
How does the voltage gated potassium channel contribute to the plateau in action potential
Channels are slower to open, usually when plateau ends and Na and Ca channels close
Muscle type with no troponin
Smooth muscle
Regulatory protein in smooth musckle which initiates contraction
Calmodulin
Small invaginations of cell membrane about the surface of the sarcoplasmic tubules
Caveolae
Membrane spanning protein used to create gap junctions in cells
Connexin
Activator and inhibitor of NMDA receptor
Glutamate - activate
Magnesium ion - inhibit
Unphosphorylated myosin bridges bound to actin
Latch bridges
Composition of water in the body, in percentage
60% water (40% ICF 20% ECF)
out of 20% (80% interstitial fluid 20% plasma)
Logic behind membrane potential (in terms of diffusion and physics)
Na higher concentratin outside, K higher inside. Diffusion from higher to lower concentration creates difference in net charge, hence membrane potential
Resting membrane potential of a normal nerve fiber
-90 mV
potential inside is more negative
Function of the Na-K pump (ions and direction)
3 Na ions pumped outside
2 K ions pumped inside
Contributory factors for resting membrane potential
Diffusion potential of K (most impt)
Diffusion potential of Na (goldmann equation)
Na-K pump (extra -4mV due to more + ions going out)
Mechanics of the voltage gated sodium channel
Resting state -entry gate closed, exit gate open
Depolarization to a voltage of -70 to -50 causes conformational change, opening entry channel, causing more sodium to go inside
Same conformational change closes the exit channel but more slowly, When it closes, depolarization ends
When resting membrane potental returns to original, exit gate will reopen
Mechanics of the voltage gated potassium channel
Closed at rest
Opens slowly when potential rises toward zero, around time when sodium channel closes
Potassium exits cell, causing repolarization
Toxin that blocks sodium channels`
Tetrodotoxin
Toxin that blocks potassium channels
Tetraethylammonium
Why is potassium conductance greater than sodium conductance at resting state
Potassium leak channels make membrane more permeable to K
Effect of hypocalcemia on sodium channels
Na channels opened by a lower increase in membrane potential - making it more excitable. In muscles, it causes muscle tetany
What is the threshold for stimulation (quantity and logic)
-65 mV - membrane potential required to start action potential
when sodium entering is more than potassium exiting
Mechanism of propagation of action potential
Inward diffusing sodium ions in a depolarizing segment also increase voltage in adjacent membrane, causing that to depolarize too. It traves in all directions until entire membrane is depolarized
Mechanics of Na-K pump
Active transport - ATP requiring
3 Na out of cell for 2 K into cell.
Returns Na and K to original positions
How does automatic membrane depolarizaition work (i.e pacemaker cells)
More permeable to Na or Ca, Resting membrane potential is equal or higher than threshold for excitation
What prevents self re-excitation in pacemaker cells?
Increased potassium conductance after repolarization causes hyperpolarization, bringing membrane potential closer to K Nernst potential (-94)
What substance in the Schwann cell membrane insulates the nerve membrane of theaxons
Sphingomyelin
Two advantages of saltatory conduction
- Faster velocity of nerve transmission
2. Less ions transferred = less energy required
Period during which a second action potential cannot be elicited even with a strong stimulus
Absolute refractory period
Effect of high extracellular fluid calcium on sodium permeability
Decreases Na permeability
Thin membrane enclosing muscle fiber
Sarcolemma
Components of myofibril? Which is thin which is thick
Actin - thin filament (acthin)
Myosin - thick filament
A band vs I band? Components and structure at middle
A band - anisotropic to polarized light - myosin and actin overlap. Mid is M line
I band - isotropic -actin only. Mid is z disk
Define a sarcomere
Portion of myofibril between two z disks
Molecule which keeps actin and myosin in place
Titin
Mechanism of muscle contraction - role of action potential, Ach, Na and Ca
Action potential to nerve ending,
acetylcholine release,
Acetylcholine gated Na channels in fiber open
Na diffuses, opening voltage gated Na channels
Action potential travels in fiber
Depolarization causes sarcoplasmic reticulum to release Ca
Ca initiates actin and myosin contraction
Ca is pumped back to SR and stops contraction
What structure generates force of muscle contraction
Cross bridges of myosin, and actin
Function of tropomyosin
Attached to active site of actin strand at resting state, inhubiting contraction
Difference bet Trop I, Trop T and Trop C
Troponin is believed to attach tropomyosin to actin
I - strong affinty for actin
T - for tropomyosin
C - for Ca
What initiates activation of actin active sites
Calcium
Mechanism of the sliding filament theory of contraction
Cross bridge head binds with ATP and cleaves it to ADP and P, releasing energy
Calcium exposes actin active sites
Myosin binds to actin and pulls actin
Bound ADP and P is released, allowing new ATP to bind
What is the Fenn Effect
The greater work performed by muscle, greater ATP is cleaved.
Sarcomere length which provides maximal tension
2.2 um
Sources of energy for muscle contraction
Phosphocreatine - cleavage of high energy phosphate bond
Glycolysis of glycogen stores (anaerobic)
Oxidative metabolism
Energy requiring processess in muscle contraction
Walk along mechannism of actin and myosin
Pumping Ca from sarcoplasm back to sarcoplasmic reticulum
Pumping Na and K in pumps
Differences bet fast and slow fibers based on
Type, color, size, innervation, blood vessel and mitochondria amount
Slow / Type 1 / Red Muscle
Small, for endurance, smaller nerve fibers, more extensive blood supply, increased mitochondria, lot of myoglobin
Fast /Type II / White Muscle
Large, for strength, extensive SR and large glycolytic enzymes for.rapid release, less extensive blood supply, fewer mitohondria, no myoglobin
Function of myoglobin
Combines with oxygen and stores it in red muscle until needed
Events starting from action potential speading to presynaptic terminal that lead to acetylcholine release in the NMJ
- Action potential spreads on terminal
- Voltage gated calcium channels open and allow Ca to move from synaptic space to interior
- Ca-calmodulin dependent kinase is activated and phosphorylates synapsin
- Synapsin anchoring Ach to cytoskeleton is freed. Vesicle moves to active zone
- Exocytosis and Ach release
Acetylcholine receptor complex subunits in fetal and adult?
Fetal - 2 alpha 1 beta delta and gamma
Adult - 2 alpha 1 beta delta ans epsilon
Acetylcholine attached to which subunit, causing thr conformational change
Alpha
What ions pass through the activated acetylcholine gated channel
Na, K, Ca
But mostly Na in motor end plate
What is end plate potential
Positive potential change after sodium influx in opened ach gated channel
Two mechanisms of removal of acetylcholine in the synaptic cleft
Destruction by acetylcholinesterase
Diffusion out of synaptic space
Effect of curare on motor end plate
Blocks ach channel attachment site
Effect of botulinum toxin on motor end plate
Decrease quantity of ach release by nerve terminal
Difference of nerve fiber and skeletal fiber in terms of
- Resting membrane potential
- Duration of action potential
- Velocity of conduction
- Resting membrane potential is almost the same
- Duration is longer in skeletal muscle by 5 times
- Velocity is slower in muscle fiber
Function of T tubules
Penetratr the interior of muscle fiber and transmits current to inside, causing Ca release and muscle contraction
Large chambers of sarcoplasmic reticulum abutting the T tubules
Terminal cisternae
Receptors linked to calcium release channels in the T tubule which sense voltage change and causes release of calcium in terminal cisternae
Dihydropyridine receptor or Ryanodine receptor
What maintains high calcium concentration in sarcoplasmic reticulum?
Calcium pump causes active transport back to SR
Calsequestrin binds to Ca in reticulum
Multi unit vs unitary smooth muscle
Multi unit - fibers contract independently of each other, controllef by nerve stimuli
Ex: ciliary muscles of eye, iris, arrector pili
Unitary - (syncytial or visceral smooth muscle) - gap junctions allow contraction as a unit.
In smooth muscle, actin is attached to which structure? (Counterpart of Z disk)
Dense bodies
Which muscles can contract a higher percentage of length? Smooth or skeletal
Smooth
Smooth muscle vs skeletal in terms of speed of myosin cross bridge cycling, energy requirement, and maximal force of contraction
Slower cycling, lower energy reqt, higher max force
Latch mechanism of smooth muscle and importance
Energy required to maintain contraction is less, allowing prolonged tonic contraction
How does calcium initiate contraction in the smooth muscle?
- Calcium entry
- Reversible binding with calmodulin
- Ca-calmodulin conplex activates myosin light chain kinase
- Kinase phosphorylates regulatory chain and activates myosin head
- Myosin head can bind with actin filament and proceed contraction
Source of majority of Ca for smooth muscle
ECF. SR only contributes some since some smooth muscle have no SR
Enzyme required for relaxation of smooth muscle -this deactivates myosin head
Myosin phosphatase - removes phosphate
Stereospecificity is characteristic of what type of diffusion
Carrier-mediated diffusion
