2. Ion channels Flashcards
Subcomponents of GABA?
5
Subcomponents of acid-sensitive channels?
3
Subcomponents of Mechano-sensitive channels?
6
Explain setup of an AMPA receptor
Consists of 4 subunits. Has 2 dimmers (1st is the red and green, the 2nd is the blue and yellow).
Mutations in the channels can lead to:
- reduced protein expression (if mutation is a the proteins)
- folding problems, leading to no correct assembly/topology; reduced transport; unstable protein
- no correct anchoring to scaffold
- altered ligand binding
- altered gating
- loss/gain of funciton
Channelopathies can be caused by
Exocytosis, Channel mutations and Autoimmune disorders
Channel types related to channelopathies
ligand gated or voltage gated
Excitotoxicity can be caused by
ischemic stroke or trauma
Penumbra
synaptic diffusion of neuronal damage –> the the primary damage causes secondary damage through excitotoxicity
How does ishemic stroke cause Excitotoxicity
Ischemia –> no oxygen to microcondria –> decreased ATP –> Na/K Pump stops working –> ionic gradient changes –> cause the sodium/calcium exchanger (brings 3 Na+ into the cell and 1 Ca++ out) to slow down, as more Na is already in the cell. Other problem with ATP going down is that the plasma membrane associated calcium ATPase pump stops sending Ca++ out of the cell.
Subconclusion: we have too much CA2+ in the cell
Ca2+ causes the vesicles to fuse to the membrane and cause exocytosis. Glutamate is now sent into the synapse, but because we have a lot CA2+, we have a lot of glutamate sent out. Glutamate receptors (NADA & AMPA) fire, so you get the movement of Na+ in (more than K+ goes in) --> leads to graded potential --> leads to voltage gated Na+ channels to open --> leads to a big depolarization. An NMDA receptor was blocked by Mg2+ because the cell was negatively polarized before. Now NMDA is un-blocked and will lead Ca2+ into the neuron --> Ca2+ in the ion goes up --> will lead to an activation of calpain --> calpain deactivates the NA/Ca2+ exchange pump --> leads to the positive feedback loop the Ca2+ will become higher and higher --> can lead to necrosis or apoptosis (voluntary death) --> will lead to the neuron sending out all it's NT's and we now have a loop (glutamate transporters reverse what they normally do and now sends out all the glutamate into the synapse)
How does the resting potential membrane form?
The membrane is more permeable to K than Na, meaning that more K is leaving the cell than Na is coming in, which leads to a lower internal change inside the cell. When we reach the resting potential, the positive ions will not want to move out of the cell as much, because they like the negative enviournment inside the cell. Because of the change in membrane potential, the membrane will be more permeable to Na now. At some point, the movement of K out and Na in will be the same (electrical equilibrium). In order to obtain a chemical equilibrium, the NA/K pump is what what reverses the movement of the ions, so it helps the chemical balance and not the electrical one.
Edema
Cell swelling (cause by unbalance of concentrations of ions)
Reactive oxygen species or oxygen radical
A type of unstable molecule that contains oxygen and that easily reacts with other molecules in a cell. A build up of reactive oxygen species in cells may cause damage to DNA, RNA, and proteins, and may cause cell death. Reactive oxygen species are free radicals. Also called oxygen radical.
phosphatidylserine
Phosphatidylserine is a fatty substance called a phospholipid. It covers and protects the cells in your brain and carries messages between them
Opsonins
Opsonins are extracellular proteins that, when bound to substances or cells, induce phagocytes to phagocytose the substances or cells with the opsonins bound
Caspase-3
Caspase-3 is a caspase protein who’s sequential activation of caspases plays a central role in the execution-phase of cell apoptosis
What does the binding of annexin V to toxine treated neurones imply?
a translocation of phosphatidylserin towards to outer neuronal, which is a marker for early apoptosis
Glutamate is important in which disorders?
Epilepsy, ischemia, Parkinson, Huntingtons, ALS, Schizophrenia
Glutamates role in Epilepsy
Glutamatergic synapses are hyperactive
Glutamates role in Ischemia
Too much glutamate - we need a blocker of glutamate receptors (NMDA subtype) prevent neuronal cell damage
Glutamates role in preventing issues in Morbus Parkinson
cell death in substantia nigra is prevented by NMDA receptor antagonists
Glutamates role in Morbus Huntington
quinolinic acid, an endogenous glutamatergic agonist, is involved in cell death in the striatum