Communication, Electrical Signalling, Channels and Transporters Flashcards Preview

PHYS5530M Physics of Biological Systems > Communication, Electrical Signalling, Channels and Transporters > Flashcards

Flashcards in Communication, Electrical Signalling, Channels and Transporters Deck (38)
Loading flashcards...
1
Q

Direct Signalling

A
  • gap junctions between cells found joining nearly all cells in solid tissues
  • -connexon in each cell membrane join together to form channel between the two cells

-cell-cell recognition, receptors on one cell surface bind to specific ligands on nearby cell initiating a cascade of events

2
Q

Non-Direct Signalling

A
  • panacrine signalling - molecules released by endocyotsis and transmitted to other cell by diffusion through extracellular fluid
  • synaptic signalling - neurotransmitter released and diffuses across synapse
  • long distance (hormonal) signalling - molecule released into blood stream, communication molecule transported in blood to other cells
3
Q

Stages of Cell Signalling

A
  • transmitting cell releases primary messenger molecules
  • received by cell membrane receptors triggering transduction
  • inside the cell, secondary messenger molecules which trigger cellular responses / change in gene expression
4
Q

Quoram Sensing

A
  • regulation of gene expression in response to changes in cell population density
  • cells release a sepcific signalling molecule constantly ase well as detecting it
  • so signalling molecules increase in concentration as a function of cell population density
  • receptors that recognise the molecules respond when a threshold concentration is reached
  • at low cell density cells exhibit individual behaviours
  • above the threshold cell density quoram sensing genes are activated enabling group behaviours
5
Q

Molecular Communication Timescales

A
  • it takes ~50s for a drop of blood to circulate the body
  • it takes ~7hrs for ions to diffuse the length of an axon by random diffusion
  • it takes ~4hrs for a molecular motor to walk the axon length
  • these are all very slow compared to the sub-second reactions observed
6
Q

Electrical Signalling (Neurons)

A
  • ions move across the membrane generating a current
  • this changes the potential across the membrane
  • if conditions are right charge flows and the potential change propagates down the axon in ms
  • diffusion wants to make uniform the concetration of ions across the membrane by diffusion but a electric potential could prevent this
7
Q

Nernst Relation

General Case

A

-consider charge distribution in the presence of a battery
-what will be the voltage for a given charge distribution:
ln[ c(L) / c(0)] = - qΔV/kbT

8
Q

Nernst Relation

Membranes

A

ΔV = - kbT/q ln[cin/cout]

-for postive ions, for negative ions: cout/cin

9
Q

Establishing Existence of Membrane Potential Experiment

A
  • electrodes inserted into giant squid axons to measure potential across membrane
  • found that positive ions were mobile across the membrane whilst negative ions tended not to be
10
Q

What happens when you have a population of mobile and immobile ions?

A
  • the mobile positive ions would like to diffuse away from the cell to make the inside and outside concentrations the same
  • but doing this pulls them away from negative ions therefore costing electrostatic energy
  • as a result an equilibrium is set up
11
Q

Setting the Membrane Potential

A
  • if some positive ions flow out:
  • -the negative charges inside are attracted to the inner membrane due to the cloud of positive charges outside that have just flowed out
  • like parallel plate capacitor with +/- q on the surface
  • this sets up the voltage difference across membrane, V given by Nernst
12
Q

Donnan Equilibrium

A

-cells have >2 species of ion and charged proteins (usually negative)
-how do all of these come to equilibrium?
-at equilibrium, by charge neutrality:
cin,tot = cout,tot = 0
-and from the Nernst relation:
ΔV = -kbT/q ln[c1+in/c1+out] = -kbT/q ln[c2+in/c2+out]
= -kbT/q ln[c3-out/c3-in]
-e.g. for three types of ion, 1 & 2 positive and 3 negative
-at equilibrium, these values can be maintained by the cell without using any energy

13
Q

Osmotic Pressure Due to Charge Imbalance

A

-at Donnan equilibrium there can be a significant concentration difference causing osmotic pressure
Δp = Δc kb T
-where Δc = cin,tot - cout,tot
-to resolve this the cell pumps (mainly Na+) ions out of the cell

14
Q

Sodium Anomaly Experiment

A
  • equilibirum predicts ΔV<0 but sodium is way off, (positive)
  • this Na+ being way out of equilibrium is refered to as the ‘sodium anomaly’
  • the large Na+ difference between in a out balances the osmotic pressure so the cell is not in equilibrium
  • it burns energy to pump Na+ out of the cell to balance osmotic pressure
15
Q

Ionic Current

A

-can describr flow of ions using Ohm’s Law:
I = V/R OR I=gV
-where g is conductance
-for ion species, i, the current flux is given by:
Ji = Ii/A = gi [ΔV - Vi,nernst]

16
Q

Membrane Conductance

A
  • there are different conductance values, g, for each ion
  • generally, Na+ is the least conductive species
  • with g(K+) ~ 25 g(Na+)
17
Q

Membrane Flux With Pumps

A

-even with ΔV=0 and cin=cout there is still current flowing due to ion pumps:
Ji = Ii/A = gi [ΔV - Vi,nernst] + ji,pump
-ji,pump are related to each other by the ratio of ions pumped in/out
-e.g. 2K+ pumped in for every 3Na+ pumped out

18
Q

Membrane Steady State

A
  • with pumps, what is the resting state of the membrane?
  • despite being out of equilibrium, the cell is in a steady state so ΔV and the concentrations don’t change in time
  • in the steady state, the fluxes of each ion =0
  • this allows ΔV to be written in terms of the ion conductance and Nernst potential for each ion
  • the rest potential, ΔV, lies nearest the Nernst potential for the most conductive ion
19
Q

Voltage Sensitive Ion Channels

A
  • if we could make Na more conductive thean K+, the potential would switch by more than 50mV
  • there are voltage sensitive ion pumps that make the membrane conductance in favour of Na+ so the potential flips which generates a voltage pulse
  • under the right conditions this voltage pulse can propagate leading to an action potential or nerve pulse
20
Q

Action Potential

Description

A
  • cell membrane starts at resting potential of -70mV
  • if the threshold potential of -55mV is reach actino potential will propagate
  • the membrane depolarises to +40mV
  • renormalisation to -80mV overshooting the resting potential
  • refactory period where the potential returns to the resting state of -70mV
21
Q

Action Potential

Resting Potential and Threshold Potential

A
  • membrane voltage is -70mV
  • inside is generally negative and outside is generally positive
  • closed voltage gated sodium and potassium channels in the membrane
  • threshold potential -55mV triggers sodium ion chanenls to open
  • sodium ions move in through channels down a concentration gradient
  • flow of positive charge into cell
22
Q

Action Potential

Depolarisation and Repolarisation

A
  • the positive charge that has come in through the sodim channels diffuses inside the cell propagating the action potential and triggering the next sodium channels to open
  • this continues to propagate down the cell
  • after 1ms, ball and chain inactivation of sodium channels - ball of amino acids attached to the channel blocks the pore
  • higher positve voltage across the membrane triggers potassium ion channels to open
  • potassium ions diffuse out of cell down their concentration gradient, this begins to equal out the charge of the sodium ions that have entered resetting the membrane potential
23
Q

How are concentration gradients maintained for future action potentials?

A
  • ion exchange pump used energy from ATP hydrolysis to pump 3Na+ out of the cell and 2K+ into the cell at a time
  • this is constantly working so that the action potential doesn’t completely deplete Na+ and K+
24
Q

Importance of Channels and Transporters

A
  • channels and transporters allow:
  • -electrical signalling
  • -chemical sensing
  • -vision
  • -hearing
  • -touch
  • -pressure
  • -temperature sensing
  • -muscle contraction
  • -release of neurotransmitters
  • -growth
  • -energy production
25
Q

Channels vs Transporters

Channels

A
  • allow ions to move across membranes down concentration gradients
  • can be opened/closed by pH, temperature, signalling molecules, change in voltage, mechanical stress etc.
26
Q

Channels vs Transporters

Transporters

A
  • physically assist small molecules across the membrane
  • ususally via input of energy (ATP) or chemical potential
  • act against concentration gradients with multiple steps / conformational changes
  • a more complex set of dynamics
27
Q

Discrete State Systems

A

-for a system at temperature T, the probability of finding the system in state with energy E:
P(Ei) = 1/Z exp(- Ei/kbT)
-where Z is the partition funciton, the sum over all energy states of the system:
Z = Σ exp(- E/kbT)
-sum over all energies

28
Q

Two State Systems

A
  • ion channels are two state systems, either open or closed
  • there is a free energy barrier associated with transition between the two states
  • the probabiltiy of a given state depends on the free energy difference between them and the temperature
  • when the states are in equilibirum flow between them in each direction is equal
29
Q

Gating Mechanisms

A

-switching between open and closed conformations requires a change in free energy at a rate depending on the free energy barrier:
Po / Pc = exp[- (Go-Gc)/kbT]
-biology tunes these free energy differences and barriers using external forces e.g. voltage, tension, interaction with other molecules, light, temperature

30
Q

Voltage Gated Ion Channels

A
  • open in response to a change in membrane potential
  • usually ion specific
  • the V_1/2 is the voltage at which the probabiltiy of being open is 0.5
31
Q

Mechanosensitive Ion Channels

A

-open in response to force e.g. membrane tension
-vital for senses such as touch and hearing
-used by bacteria to regulate turgor pressure in response to changes in external osmotic pressure
-

32
Q

Ligand Gated Ion Channels

A
  • open in response to binding of a chemical messenger e.g. neurotransmitter
  • involved in communication between synapses, taste and smell
  • probabiltiy of opening depends on the concentration of the ligand
33
Q

Polymodal Ion Channels

A

-single ion channels modulated by multiple stimuli

34
Q

Selectivity Filters

A
  • narrowest part of the channel is lined with amino acid residues that interact with the passing ions and mimic the arrangement of water molecules for the specific ion
  • in order to pass through each ion has to shed its water molecules
  • dimensions of the channel minic the shell of water
35
Q

Types of Transporter

A
  • ATP pumps - couple ATP hydrolysis with movement of ions across a membrane against the concentration gradient
  • symport - uses energy already stored in ion gradients to move a molecule across the membrane with some ions
  • antiport - same as symport but ions move in the opposite direction to the target molecule
36
Q

Molecular Mechanisms of Transporters

A
  • rocker switch - substrate binds between two domains catalysing the rearrangement of the two domains around the central binding site to allow the substrate move into the other side of the membrane
  • rocking bundle - one structurally disimilar domain rearranges against a less labile domain
  • elevator model - one domain moves against another relatively rigid domain to physically translocate the substrate across the membrane
37
Q

Experimental Techniques to Determine Physical Protein Structure

A
  • x-ray crystallography
  • cryo-electron microscopy
  • NMR
38
Q

Experimental Techniques for Observing Protein Dynamics

A
  • single ion-chanel recordings
  • FRET
  • high speed AFM