Lecture 2 - Membrane Permeability, Cell Volume and pH Regulation; ATP Dependent Ion Pumps and Ion Exchangers Flashcards
What molecules can pass through membranes?
Hydrophobic molecules
Small, uncharged, polar molecules
What molecules can’t pass through membranes?
Large, uncharged, polar molecules
Ions
What is passive diffusion?
Dependent on permeability and concentration gradient
Rate increases linearly with increasing concentration gradient
What is facilitated diffusion?
Permeability for substance is increased by incorporation of a specific protein in the bilayer.
What is active transport?
Transport of ions or molecules against the favourable concentration gradient
Energy may be required depending on concentration gradient and electrochemical gradient
What is a cotransporter?
Membrane transporter that transports more than one molecule.
What is uniport?
One molecule is transported in one direction.
What is symport?
Two molecules are transported in the same direction.
What is antiport?
Two molecules are transported in opposing directions.
What is Na K ATPase?
Plasma membrane associated pump
Uses ATP to pump ions
P type ATPase
What is the structure of Na K ATPase?
alpha subunit - binding site for K, Na, ATP and ouabain
beta subunit - glycoprotein directs pump to surface
What does ouabain do?
Binds to alpha subunit - inhibits Na K ATPase.
What does Na K ATPase do?
Uses energy from ATP hydrolysis
moves 2K into the cell
moves 3Na out of the cell
forms Na and K gradients
what does Na K ATPase driving secondary active transport do?
control of pH regulation of cell volume regulation of Ca concentration absorption of Na in epithelia nutrient uptake
what is the function of K channels?
allows K diffusion down the concentration gradient set up by Na K ATPase
mainly responsible for membrane potential
what is the resting membrane potential?
-70mV
what is the role of Ca ATPases?
control of resting Ca concentration
uses ATP to pump ions by active transport
what is the role of pmca?
Expels Ca from the cell, high affinity, low capacity
what is the role of serca?
Accumulates Ca in the SR/ER, high affinity, low capacity
what is the role of ncx?
Inward flow of Na down its concentration gradient drives outward flow of Ca up its concentration gradient, low affinity, high capacity
what happens to ncx in ischaemia?
atp is depleted in ischaemia Na K ATPase is inhibited Na accumulates in cell leading to depolarisation ncx reverses Na moves out, Ca moves in high Ca is toxic
what is the role of nhe?
Inward flow of Na down its concentration gradient leads to cell alkalisation by removing H
what is the role of nbc (sodium bicarbonate cotransporter) and Na dependent Cl HCO3 exchanger?
acid out base in uses Na gradient set up by Na K ATPase raises intracellular pH regulates cell volume
what is the role of ae (anion exchanger) and Cl HCO3 exchanger?
base out
acid in
cell volume regulation
how is cell swelling reversed?
extrude ions
how is cell shrinking reversed?
influx ions
what are osmotically active ions?
Na
K
Cl
organic osmolytes (amino acids)
how is bicarbonate reabsorbed in the proximal tubule?
Na K ATPase keeps intracellular Na low so nhe can pump H into the proximal tubule lumen
H picks up bicarbonate in the lumen and brings it back into the cell
what do loop diuretics do?
block Na reuptake in the thick ascending upper limb
what does amiloride do?
acts in distal convoluted tubule (ENaC) and proximal convoluted tubule (Na/H) to prevent Na reuptake
what does aldosterone do?
upregulates these transporters
what does sprionolactone do?
glucocorticoid receptor antagonist - used to treat if aldosterone is high
why does cystic fibrosis cause thick mucous?
normally transport of Na out of the cell by Na K ATPase allows for symport of Cl into cell with Na and K
faulty ctfr protein leads to accumulation of Cl in cell
water moves into the cell via osmosis leaving thick viscous mucous in the lumen
what happens in diarrhoea?
ctfr is overly active once phosphorylated by pka
Cl is excessively transported into lumen
water follows leading to symptoms of diarrhoea
How does water move across membranes?
Osmosis
What increases a membrane’s permeability?
Specific channels
What is the difference in Cl permeability in a phosphatidylserine bilayer compared with an erythrocyte membrane?
10^7 fold.
What protein is responsible for Cl transport?
Band 3
What does the Band 3 protein do?
Carries out the specific exchange of Cl for HCO3.
What does a ligand gated ion channel do?
Open or close in response to ligand binding to a receptor site.
What does a voltage gated channel do?
Open or close in repsonse to potential difference across the membrane.
What does a gap junction do?
Close when cellular calcium concentration rises above 10 micromoles or the cell becomes acid.
What determines whether a molecule moves by passive or active transport?
The free energy change of the transported species.
How is the free energy change of the species determined?
The concentration gradient for the transported species and the electric potential across the membrane when the species is charged.
Where does the free energy driving active transport come from?
Directly or indirectly from the hydrolysis of ATP
What drives ATP synthesis in mitochondria?
A gradient of H+ ions via an ATP dependent proton transporter.
What is secondary active transport?
The transport of one substance is linked to the concentration gradient for another via a cotransporter, so hydrolysis of ATP is used indirectly
What is the role of the Na glucose co transport system of the small intestine and kidney?
Entry of sodium provides the energy for entry of glucose
What is the role of mitochondrial Ca uniports?
Operate at high Ca concentration to buffer potentially damaging concentrations
When cellular buffering capacity is exceeded, how is cellular pH controlled?
Plasma membrane transporters
How is acidification opposed?
Expelling H+ or inward movement of bicarbonate ions
How is alkalinisation opposed?
Expelling bicarbonate via the anion exchanger
What does electroneutral transport of ions allow?
The osmotic strength of the cytoplasm to be varied without affecting the membrane potential
