Unit 2 Flashcards
Higher intra/extracellular?
Sodium, potassium, chloride, phosphate, protein
Intra - potassium, phosphate, protein
Extra - Sodium, chloride
What type of molecules can diffuse freely through the cell membrane?
Lipid
Name examples of substances that dissolve directly through the lipid bilayer (4)
Oxygen, nitrogen, C02 and alcohols
How do simple and facilitated diffusion compare/contrast?
Simple diffusion dependent on lipid solubility of substance, linear relationship with concentration
Facilitated diffusion depends on Vmax of substance, normally faster initially, then plateaus - limited by maximum rate of conformational change of carrier protein
What is the formula for net diffusion?
Net diffusion is proportional to the concentration of a substance outside a membrane, minus the concentration of the substance inside the membrane
What is the Nernst potential?
The electrical difference that will balance a given concentration difference of univalent ions at normal body temperature
What is the Nernst equation?
EMF(mV) = +/-(61/z) x (logC1/C2)
z = electrical charge of ion
What factors effect net diffusion?
Concentration, electrical potential, pressure
What determines osmotic pressure?
The number of particles per unit volume
How does the Na-K pump work? What is it’s main function?
3xNa+ pumped out of cell in exchange for 2xK+
Regulates cell volume
Describe the electrogenic nature of the Na-K pump
Because 3 Na and removed from the cell in exchange for 2 K+, there is a net positivity outside the cell and negativity inside the cell
How does calcium concentration compare inside/outside the cell? How is it maintained?
Intracellular calcium concentration very low
2 calcium pumps, one pumps calcium outside the cell, the other pumps into intracellular organelles (SR in muscle, mitochondria other cells)
Name 2 examples of primary active transport of hydrogen ions?
Gastric glands of the stomach
Late distal tubules and cortical collecting ducts in kidneys (intercalated cells)
If it takes 1400 calories to concentrate 1 osmole of a substance 10-fold, how much would be needed to concentrate it to (a) 100-fold and (b) 1000-fold?
a) 2800
b) 4200
What is the resting membrane potential of large nerves?
-70mV
What factors contribute to the negative resting potential of cells?
Increased permeability of cell membrane to K+, allows K+ to leak out - main contributor
The 3Na-2K pump - more sodium removed from cell than potassium in
What are the stages of a neuron action potential?
Resting stage
Depolarisation - voltage-gated sodium channels open, membrane becomes permeable to sodium ions, flood in and depolarisation
Repolarisation - sodium channels close, voltage-gated potassium channels open, potassium moves out, repolarisation
Describe the opening, closing and re-opening of voltage-gated Na channels
When resting membrane potential becomes less negative, channel is activated. The same increase in voltage causes inactivation a few seconds later
Channel will not re-open until membrane potential returns to near the original level
Describe the opening of the voltage-gated potassium channels
Activated when membrane potential rises, however, slight delay so open as sodium channels close
What is the role of calcium in the generation of an action potential?
Voltage-gated slow calcium channels - contribute to depolarisation, produce more sustained depolarisation
Where are calcium channels most numerous?
Smooth muscle and cardiac muscle
How does the concentration of calcium ions in the ECF effect depolarisation?
When there is a deficit of Ca++, sodium channels are opened by smaller increase in membrane potential
Which cells produce myelin?
Schwann cells
What is the name for the notches in myelin?
Nodes on Ranvier
What is the function of the nodes of Ranvier and what are the benefits (2)?
Allow saltatory conduction
1 - increased velocity of nerve transmission
2 - requires less energy
Describe the microscopic structure of skeletal muscle
Light bands - actin only - I bands
Dark bands - actin and myosin - A bands
Z disks - actin attach
Region between Z disks = sarcomere
Titin - maintains side-by side relationship of actin/myosin
Space between myofibrils filled with sarcoplasm
What is the content of the sarcoplasm?
K+, Mg++, PO4-, mitochondria
Describe the general mechanism of muscle contraction
Action potential travels along motor nerve
ACh secreted
ACh acts on muscle fibre membrane - opens ACh-gated cation channels - Na influx => action potential
Action potential causes sarcoplasmic reticulum to release Ca++
Describe the structure of myosin
6 polypeptide chains, 2 heavy, 4 light
Heavy chains wrap around each other to form helix, ends folded into head
Light chains form part of head
Myosin molecules bundled together with a twisted axis
Describe the structure of actin
Backbone - double stranded F-actin, each strand polymerised G-actin
Each G actin molecule has ADP attached - active site for cross bridge interaction
Tropomyosin - wrapped around F actin - lie on top of binding sites in resting state
Troponin - TI - affinity for actin
- TT - affinity for tropomyosin
- TC - affinity for Ca++
What activates actin?
Ca++
Describe the relationship of ATP/ADP and the power stroke of the myosin head
ATP binds myosin head - ATPase - ADP + PO4
Binds exposed actin site - power stroke, ADP released
ATP binding causes myosin head detachment
ATP cleaved - head re-cocked
What are the 3 sources of energy for muscle contraction?
Which of them need O2
Which is the main contributor to long term muscle contraction?
1 - phosphocreatine (O2)
2 - glycolysis
3 - oxidative metabolism (O2) (MAIN CONTRIBUTOR)
What are the features of slow muscle fibres?
Small, small nerve fibres, extensive blood supply, lots of mitochondria, large amounts of myoglobin
Describe ACh secretion in the NMJ
Action potential
Voltage-gated Ca++ channels open
Ca++ influx
Ca-calmodulin-dependent protein kinase activation
Phosphorylation of synapsin proteins (anchor ACh vesicles)
Free ACh vesicles dock at release sites and empty via exocytosis
What ions are transmitted through ACh channels?
Positive only (strong negative charge in channel)
Sodium flows most - negative charge inside cell pulls in
How/where is ACh formed?
Vesicles formed in Golgi
ACh formed in cytoplasm, immediately transported into vesicles
What is ACh split to by acetylcholinesterase? What happens to the substances?
Acetate + choline
Choline actively reabsorbed to form more ACh
How are vesicles formed for repeated NMJ transmission?
After each action potential coated pits appear (formed by contractile proteins - clarithrin) and break away to form new vesicles
What is the MOA of neostigmine?
Inactivates acetylcholinesterase
What is the pathophysiology of myasthenia gravis?
Autoantibodies produced that block or destroy ACh-r
In what 3 ways do action potentials in skeletal muscle differ from in neurone?
Lower resting potential (-80-90mV)
Longer duration
Slower velocity of conduction
How do action potentials spread across muscle fibres?
Across surface, penetration through transverse (T) tubules
How does an action potential lead to calcium release in a muscle fibre?
Action potential sensed by dihydropyridine receptor, linked to calcium release channel (ryanodine receptor channel) in the sarcoplasmic reticulum
How is calcium concentration in the sarcoplasmic reticulum achieved?
SERCA pump - constantly active
Calcium-binding protein in SR - calsequestrin
What is the MOA of dantrolene?
Antagonises ryanodine receptor, inhibits calcium release from the SR
What are the two types of smooth muscle?
Multi-unit - eg cilia/iris
Unitary - most viscera in body
What is the main difference between smooth and skeletal muscle?
No troponin complex in smooth
Briefly, how are smooth muscle fibres organised?
Actin filaments connected to dense bodies, with myosin fibres interspersed between
What are 6 differences between smooth muscle contraction and skeletal?
Slow cycling of myosin cross-bridges
Low energy requirement
Slow onset
Greater force of contraction
Latch mechanism
Stress-relaxation
How is smooth muscle activated?
Smooth muscle contains calmodulin rather than troponin
Ca++ binds to calmodulin
Ca-calmodulin activates myosin light chain kinase
Phosphorylates regulatory myosin head - while phosphorylated capable of repeated binding
What is the source of calcium for SM contraction?
Extracellular (poorly developed sarcoplasmic reticulum)
What regulates the force of SM contraction?
Extracellular calcium
What causes SM relaxation?
Ca pump removes calcium, myosin phosphatase reverses phosphorylation of myosin head
What is the action potential of SM?
-50-60mV
What are the two types of action potential in unitary smooth muscle?
Spike potentials
Action potential with plateau
How do smooth muscle action potentials differ from skeletal muscle?
Far more voltage-gated calcium channels, fewer sodium
Mainly generated by Ca influx, slower to open and remain open longer than Na channels
