K^+, Na^+ and Ca^2+ channels Flashcards
How many different voltage gated K^+ channels are there?
App. 40 (Shaker family)
Describe the topology of Kav.
Homomeric tetramer. Each monomer: 6 TMs + 1 re-entry loop (p-loop). C- and N-terminus are intracellular. The S4 is the voltage sensing domain. The S5-6 + the P-loop make up the pore. The P-loop is the selectivity filter. There’s a ball and chain region on the N-terminal, involved in the inhibition of the channel.
How does the voltage sensing domain (VSD) work?
Moves up 10-15 Å, rotate 90 degrees and tilts 15 degrees. It also changes conformation from a 3_10 helix into an alpha-helix. The movement of the S4 pulls the S4-S5 linker and moves it away from the pore, bending the S6 and opening the pore.
The VSD consists of…
conserved positive aa residues.
Describe how the selectivity filter works.
The ions have a hydration shell made of water molecules, that turn their partly negative oxygen molecules toward the positive ions in the filter. The water molecules have to be removed in order for the ion to cross the channel, which costs energy. But the energy is restored when the ion makes similar bondings with the carbonyl group of the protein backbone.
What makes the selectivity?
Specific aa residues in the P-loop define the selestivity of the channel for a given ion. The backbone of the aa sequence forms the selectivity, but the sidechains position the backbone, and are therefor the reason of this seletivity.
Describe BK channels.
Big K^+ channels: mainly axonal and presynaptic. Voltage - and intracellular Ca^2+ gated. Inhibits Ca^2+ channels.
Describe the inward rectifier K^+ channels.
No voltage sensing domain (indirect voltage dependence). Only 2 TM regions + P-loop (pore domain (PD)). Regulated by small substances and proteins. Have a greater tendency of letting K^+ into the cell. High conductance at negative voltages (more or less closed at -40 mV)
Describe GIRKs.
G-protein-gated IR K^+ channels. Activation of GIRK leads to hyperpolarization and inhibition.
What is the K_ATP channel (another KIR) involved in?
Insulin release: close when ATP conc. are high in cytosol leading to gating of voltage gated Ca^2+ channels resulting in insulin release.
Describe transient receptor potential (TRP) channels.
6 TMs, most are not voltage sensitive, and they are nonselective cation channels. Intracellular N- and C-terminus.
Describe cyclic nucleotide gated (CNG) channels.
Tetrameric, each monomer: 6 TMs, intracellular C- and N-terminus, C-teminal binding the CN. Pore between S5-6.
Describe the voltage gated H^+ channels.
Homodimer consisting of two voltage sensing domains (KvC). H^+ efflux.
How many different voltage gated Na^+ channels and voltage gated Ca^2+ channels are there?
10 of each
Describe the topology of the voltage gated Na^+/Ca^2+ channels.
Monomer consisting of 4 domains resembling one monomer of the Kv channel. Inactivating motif (IFM) on the linker between D3 and D4.
