Excitability and Ion channels I Flashcards
What is Electrical Excitability? (2)
Property of a cell (esp excitable cells - like neurons + muscle cells) that allow them to generate + propagate electrical signals known as A.P.’s (/nerve impulses/electrical signals)
What is Electrical Excitability closely related to? (2)
- movement of ions across cell membrane
- Changes in membrane potential
What are the 2 main factors regarding K+ electrical excitability? (2)
- K+ conc gradient
- positive charge of ion
What is a concentration gradient? (2)
ratio of ions inside and outside a cell - which helps determine the equilibrium potential
What does a high conc gradient inside a cell mean and vice versa? (2)
ions from a region of high conc to low conc, across a partially permeable membrane
so cells will leave the cell in this e.g., or cells will enter the cell in the opposite.
What does a positive charge mean and what does it do? (2)
The ions are attracted to the negatively charged interior of the cell (electrostatic attraction). This attraction will pull positive ions into the cell.
What is Ek? (2)
The equilibrium potential of the ion (i.e. K+ ek) = the net movement of ions across the membrane is 0
What is the Ek of K+ and why is it important? (3)
-70 to -90mv (in most excitable cells)
It is one of the key factors that establish the resting potential in excitable cells
plays a critical role in the generation + propagation of A.P.’S.
Define Reversible Tension/ Nerst Potential (3)
The membrane potential where the chemical and electrical gradients of ions, across a biological membrane, are in equilibrium.
There is no net flow of ions across the membrane.
It is written as Eion e.g. Ek for potassium equilibrium
How do you calculate the Equilibrium Potential? (2)
Using Nernst equation
Ex = (RT/zF)ln ((X)out)/(X)in)
What is Ex? (1)
The equilibrium potential for any given ion (i.e. ek = K+)
What is electrophysiology used for? (1)
It is used to measure the potential difference b/w an electrode inside a cell and an electrode outside a cell.
Whole cell patch clamping explained (2)
1) For these types of recordings, a single electrode is placed inside a cell where we can seal the electrode onto the outside of the cell and rupture the membrane = electrical control
2) measure membrane resting membrane potential + active/passive electrical properties of the cell (e.g. A.P. shape + firing patterns)
What maintains the Resting Membrane Potential? (2)
It is often maintained by potassium leak currents (K+ leak channels = often called the K2 or otherwise referred to as the K2P family)
but also the inwardly rectifying potassium channels
When a membrane potential reaches it’s threshold… (6)
voltage gated sodium channels are activated = cascade of effects = more voltage gated sodium channels are activation
After, the sodium channels inactivate = slower action = voltage gated potassium channels begin to open (causing an overshoot = afterhyperpolarisation)
Ends with re-established resting membrane potential
What is the resting membrane potential? (2)
The electrical potential difference across the cell’s plasma membrane when the cell is not actively transmitting signals.
It’s primarily determined by the selective permeability of membrane to different ions, specifically potassium, sodium and chloride.
What are the main components of a Voltage gated channel and what do they do? (10)
voltage sensor: identifies changes in the membrane potential
selectivity filter: determines which membranes determine which ions flow through the membrane
pore: allows the flow of ions
gate: can be opened and closed
anchor protein: vary slightly per each cell type
K2P family structure (‘leak channels’) (4)
4 transmembrane domains: M1-M4
2 pore domains: P1 + P2
2 extracellular cap helixes: C1 + C2
Functionally: K2P channels assembles dimers - contrast to other K+ channels that are tetramers
How are the K2P family regulated? (4 + 3)
- Mechanosensitivity (increased pressure opens channels) ==> contraction of the cell during hyperosmolarity leads to reduction in this current but expansion of cell by applying pressure leads to opening of these channels)
- Polyunsaturated fatty acids e.g. arachidonic acid (activate channels - but FA have X effect)
- Thermosensitivity (TREK1 activated - gradually + reversibly in response to the elevation to ambient temps (14-42°) - more steeply b/w 22-42°)
- pH, G proteins + partner proteins
What is different about K2P compared to K+, Na+ and Ca2+ channels? (2)
They don’t have a specialised voltage sensing domain + don’t show any activation during depolarisation voltage steps (except TWIK-2)
= * They are voltage insensitive (except TWIK-2)
What do K2P channels do? (1)
leak channels allow the bidirectional movement of ions up to the point of equilibrium potential (-70 to -90mv)
How many inwardly rectifying K+ channels (Kir/Kirk) are there and how are they regulated? (2)
15 channels
regulated by intracellular signalling molecules (e.g. G proteins or ATP)
KIRK channels properties + how does it work? (3)
each subunit consists of 2 transmembrane domains = form tetramer
predominantly allow the flow of K+ ions into the cell at negative membrane potentials (pushing k+ against electrical gradient = depolarise membrane)
= contribute to stabilising the rest of the membrane potential + controlling cell excitability
What are 2 well studied A.P. cells (2)
- CA1 pyramidal cells (glutamatergic ‘principal cell)
- Oriens-Lacunosum molecular interneuron (GABAergic interneuron)
