Jon Turner week 7-9 Flashcards
6 nov wut?
wutwut wtf jon
what is the difference between pores and channels?
pores are always open, channels are gated.
describe the structure of channels.
inner vestibule - between selectivity filter and gate
outer vestibule - outside selectivity filter.
gate
selectivity filter in the middle.
what are ion channels all made of?
proteins, polypeptide chains.
describe the selectivity filter on a Na channel.
Short, wide pore - inner ring of DEKA (Asp, Glu, Lys, Ala) side chains - net charge: -1
Outer ring of EEMD (Glu, Glu, Met, Asp) - helps stabilizes waiting ions - net charge: -3
describe the selectivity filter on a Ca channel.
Again a short, wide pore containing a ring of EEEE (Glu) side chains - net charge: -4
Outer ring of DSED (Asp, Ser, Glu, Asp) - again helps stabilizes waiting ions - net charge: -3
describe the selectivity filter on a K channel.
Tube of 4 x TVGYG (Thr, Val, Gly, Tyr, Gly) - all relatively neutral residues with no side chain present in the narrow pore - weak charge
what are the states of a channel?
open/closed - open state allows ion transfer.
transition - between the states this is referred to as gating.
what is gating?
the transition between open and closed/vice versa.
how is generalized gating achieved?
Twisting, tilting or bending of subunits and trans-membrane spanning α-helices (much of α-subunit around the pore region).
describe mechanical distortion
Opened by distortion of the plasma membrane (mechano-sensitive).
↑ opening induced either directly or through mechanical linkage to the cytoskeleton.
Sensory transduction in sense organs such as cochlea and skin by TRP channels. Also some “leakage” K+ and Cl- channels
difference between activation, deactivation and inactivation?
activation and deactivation are open/closed.
inactivation is permanently shut.
deinactivation is undoing of this.
describe inactivation/deinactivation.
localized:
Either a region in pore wall or close to it alters conformation physically occluding the pore
Or the selectivity filter changes conformation, reducing ion transfer.
Involves a relatively short amino acid sequence.
OR particle induced:
A free intracellular region of the channel protein that plugs the pore; a.k.a. “ball and chain” gating.
Involves a relatively long amino acid sequence or subunit.
origins of the resting K membrane permeability?
Julius Bernstein 1902, Halle, Germany (long before anyone knew ion channel existed! Had to wait until late 1970’s, early 1980’s)
Proposed the “membrane hypothesis”
Membrane was ion-selective for K+ and so K+ was the most likely ion to be responsible for RMP as:
- extracellular K+ concentration was known to be low
- indirect evidence pointed to RMP being negative
1st person to apply the Nernst equation to excitable cells:
not proved until intracellular recordings were invented.
how did hodgkin and horowicz test the membrane hypothesis?
Modified EK+ by changing [K+]o
Intracellular recording from a frog muscle fibre @18°C
Record RMP at varying [K+]o
Should obey the Nernst eq.
Result:
>10mM [K+] data fitted by Nernst eq.
K+ channels contribute background ion permeability for RMP >10mM
how do ion channels vary in ion selectivity?
sign and density
+ -
2+ +
is selectivity relative or absolute?
relative.
K channels allow Na to pass, if exta/intracellular K was removed they would become Na channels.
what is an equivalent circuit?
An equivalent circuits is a theoretic circuit that retains the properties of whatever is being modelled in its simplest electrical form
Associates membrane currents with specific ion channels with Eions and their conductances as well as the membrane’s capacitive properties
describe a battery or ion pump
Represents the electrochemical ion gradient - a source of electrical energy (equivalent to a power source or battery)
Batteries generates a voltage known as electromotive force (emf)
For each set of ion channels:
emfion = Eion
Force that drives Iion is the driving force or voltage relative to Eion i.e. the difference between the measured transmembrane voltage Vm and Eion:
Vm - Eion
larger driving force = larger current
Units: Volt (V)
DRAW ALL DESE OUT
describe conductance and resistance
Represents the ion channel permeability - a measure of how readily a current will pass through a material (G).
therefore opposite of resistance (R), a measure of how much the material opposes the flow of current
Assigned Units: Siemens (S) or ohm-1 (Ω-1)
Represented as a variable (left) image rather that a constant (right) image
what is capacitance?
Capacitors are devices that store charge
Capacitance is a measure of that ability
Capacitance (C) = stored charge(Q) / voltage(V)
Two conductors separated by a non-conductive material -dielectric/insulator
LIKE A MEMBRANE GEDDIT
Intracellular and extracellular fluid are the conductors, the membrane is the dielectric that maintains charge separation
Units: Farad (F)
how does potential difference change the stored charge if there is capacitance in a system?
increase -> increase
decrease -> decrease
what is a capacitance current?
current required to charge/discharge areas adjacent to the membrane
what determines total capacitance?
surface area of a cell membrane.
bigger = bigger