L3 Ion Channels and transporters Flashcards
a) What type of molecules can get through the lipid bilayer?
b) What type of molecules can’t?
a) hydrophobic molecules such as O2, CO2, N2 and benzene as well as small uncharged polar molecules such as h20, urea and glycerol
b) Large uncharged polar molecules such as glucose and sucrose are too big and charged molecules (ions) such as H+, Na+, K+, Ca2+, Mg2+, Cl- and HCO3-
What is a permeability constant?
Calculated values that determine the speed at which a substance crosses the lipid bilayer (the higher the value, the faster the speed and hence the more permeable)
a) Difference between passive and active transport?
b) Types of Passive transport
a) Passive- no energy required and movement is down a concentration gradient (-∆G)
Active- energy is required (atp) and movement is against a concentration gradient (+∆G)
b)
- Diffusion
- Facilitated diffusion: through a protein channel eg. ion or voltage gated channels (open due to a stimulus)
- Osmosis
What is the ionic distribution between the ECF and ICF in a 70kg man?
TBW = 60/100 of 70 = 42 Litres
UPGRADE
What is flux?
Describes how fast a solute moves- the number of mole crossing a unit area of membrane per unit time (moles/cm2/s)
What happens with the diffusion of 2 solutes?
Each substance diffuses down its own conc gradient independent of the conc gradients of other substances.
What is osmosis?
Diffusion of water from a hypotonic solution (high WP) to hypertonic (low WP) across a semi-permeable membrane.
What is a semi-permeable membrane?
Is a membrane that regulates the the transport of materials by acting as a filter allowing some particles to pass or not according to size, solubility, electrical charge, or other chemical or physical property.
What would happen if a cell was placed in a:
a) Hypertonic solution
b) Isotonic solution
c) Hypotonic solution
a) The concentration of solutes is higher outside the cell and so water will flow out of the cell, by osmosis, causing the shell to shrivel.
b) the concentration of solutions is equal inside and outside the cell and so is in equlibrium.
c) The concentration of solutes is lower outside the cell (higher inside the cell) and so water will enter the cell by osmosis, causing the cell to swell and burst (lysis)
a) What is an osmole?
b) What is osmolality?
a) Measure of a solutions ability to create osmotic pressure and affect movement of water. It is proportional to the no. of osmotic particles formed in solution
b) It is a function of the concentration of particles in solution (expressed in mOsm/kg)
a) What is the normal osmolality of plasma, interstitial fluid and the intracellular fluid?
b) How can you estimate a patients serum osmolality and why?
a) 280-310 mOsm/kg or mmol/L
b) doubling serum sodium because Na+ always has Cl- attached and each is independently osmotically active
What would the patients osmolality be if their plasma concentrations were the following:
- Sodium = 140mmol/L
- Potassium= 5mmol/L
- Urea = 5mmol/L
- Glucose= 5mmol/L
300mOsm/kg
How can you explain the rapid diffusion of water possible in some cells which is faster than diffusion across the membrane should allow?
- Aquaporins (AQP)- Integral membrane proteins
- They are a channel for transfer of h20 and urea
- contain 6 transmembrane alpha helix proteins
- inner cavity lined with hydrophilic AA
- at the centre there is + charged residues which prevent movement of charged ions so they don’t distrupt ion gradients
- still uses osmosis as depends on conc gradient
What are the types of faciliated diffusion methods?
- Ligand gated ion channels:
e. g. Ach binding to ach receptor so that sodium ions enter the channel (Nicotinic ach receptor)
e. g. ATP sensitive channel, Atp binding closes channel - Voltage gated ion channels- voltage sensor inside structure and membrane depolarisation affects it
Active or passive transport- what is it dependent on?
Dependent on the electrochemical gradient:
a) Chemical gradient: difference in solute concentration across a membrane - will be passive if down concentration gradient and active if against concentration gradient
b) Electrical gradient: difference in charge across a membrane membrane potential- passive if down electrogradient and active if against - have to look at charge of particles and charge on side of membrane
What are the roles of transport processes?
- Maintenance of intracellular pH
- Maintenance of ionic composition
- Regulation of cell volume
- Generation of ion gradients for electrical excitability of nerves and muscles
- Extrusion of waste products of metabolism and toxic substnaces
- Concentration of metabolic fuels and building blocks
Difference between Primary active transporters and secondary active transporters?
Primary- directly uses a source of chemical energy e.g. ATP to move molecules across membrane
Secondary- uses electrochemical gradient set up by Primary AT store energy to move substances across membrane
Define the following terms:
a) Uniport
b) Symport
c) Antiport
d) Co-transport
a) Transport of only one ion or molecule on a membrane transporter in one direction
b) Transport of 2 or more ion or molecules on a membrane transporter in one direction- uses co-transport
c) Transport of 2 or more ions or molecules on a membrane transporter in opposite directions - uses co-transport
d) Cotransport is the name of a process in which two substances are simultaneously transported across a membrane by one protein- Symport and Antiport
Examples of Primary active transporters
- PMCA- Plasma membrane calcium ATPase
- ATP synthetase
- Na+ pump (Na+-K+-ATPase)
What is the Na+/K+- ATPase (Na+ pump)?
- Antiport: 3 Na+ ions expelled for every 2K+ ions that enter
- Uses ATP- Primary AT
- maintains cellular concentrations of Na+ and K+
- Main function is to generate ion gradients that are used to allow secondary active transport and action potentials
Why is the control of intracellular Calcium ion concentration important?
A high intracellular Ca2+ concentration is toxic to cells
Examples of secondary active transporters?
- Na+-H+ exchanger
- Na+-Ca2+ exchanger
- Na+-glucose co-transport
What is the Na+-Ca2+ exchange? (NCX)
- 3 Na+ in the cell, 1 Ca2+ outside the cell
- Antiport
- Low affinity, high capacity
- secondary
What is the Na+-H+ exchange?
- Na+ inward flow down its concentration gradient leads to cell alkalinisation by removing H+
- antiport
- secondary
What is the Na+-glucose co-transport?
- secondary
- symport: entry of Na+ provides energy fort he entry of glucose against its concentration gradient
- small intestine and kidney
Outline how the transporters are affected in:
a) Cystic Fibrosis
b) Diarrhoea
CFTR is a chloride ion channel protein found in epithelial cells
- normal function is to transport Chloride ions into the lumen, water follows osmotically
- Chloride ions enter via na+K+2cl-
a) In CF- CFTR gene mutated leads to dysregulation of fluid in epithelial cells of lungs- leads to thickened mucus
b) In Diarrhoea (induced by Cholera) the CFTR channel is hyperactivated
Why is the Na+-K+-ATPase pump so important?
Forms Sodium and potassium gradients which are:
- neccessary for electrical excitability
- drive secondary AT –> controls IC ph, regulate cell volume and IC ca2+ conc, absorption of Na+ in epithelia and important for nutrient uptake e.g. glucose from Small intestine
Outline the transporters involved in the control of resting intracellular Calcium concentration
These transporters are removing calcium ions out of the cytoplasm into organelles or into extracellular space.
Primary Active transporters: both have high affinity but low capacity for Ca2+, removes residual Ca2+)
- PMCA (Plasma membrane Ca2+-ATPase)
- SERCA (Sarcoendoplasmic reticulum Ca2+-ATPase)
Secondary AT: Low affinity but high capacity for Calcium ions and hence removes most of these ions
- Na+-Ca2+- exchange (NCX)
Facilitated transport:
- Mitochondrial Ca2+ uniports- operate at high calcium concentration to buffer potentially damaging calcium concentrations
How is the Sodium Calcium exchanger important clinically?
- It plays a role in Ischaemia
- Normally: pumps 3Na+ inside the cell and 1 Ca2+ outside the cell
- when membrane potential is depolarised it reverses the mode of operation
- During Ischaemia, sodium pump is inefficient, ATP is depleted and so Sodium accumulates inside the cell, depolarises the cell, causing NCX to reverse and there is a high influx of calcium ions inside the cell
What ion transporters are involved in:
a) Acid Extrusion
b) Alakli Extrusion
a)
- Na+/H+ exchanger (NHE) - removes h+ from cell
- Na+- bicarbonate-chloride-cotransporter (NBC) - acid out base in
b)
- Cl-/HCO3- exchanger (AE)- anion exchanger- removes base
Why is coordination of intracellular important clinically?
ph is held at a set point intracellularly and any drift away from this ph is corrected by the increased activity by the ion transporters- drugs/medicines can be made that target these processes to treat certain illnesses.
How is ion transporters involved in cell volume regulation?
- They involve the transport of osmotically active ions i.e.- water will follow via osmosis as a gradient is created
- if a cell swells- ions will need to be extruded
- if a cell shrinks- there will need to be an influx of ions
Why must the method for cell regulation be electroneutral?
So that they dont stimulate any uncessesary action potentials
How is the PMCA (Plasma membrane calcium ATPase) used in calcium regulation?
- Expels one Calcium ion out of the cell and replaces it with a hydrogen ion that was released from Sarcoplasmic reticulum via SERCA
- primary ATP- uses ATP
- Antiport
What is the SERCA?
- takes up one calcium ion from inside cell and releases one hydrogen ion from ER
- primary AT as uses ATP
