LEC16: Ligand-Gated Channels Flashcards
what differentiates channels, by structure, from carrier proteins?
1) contain a water-filled pore through which ions travel, **strictly down electrochemical gradienst **
2) don’t bind solutes to be transported
3) don’t operate in cycles
4) DO undergo conformational changes to toggle btwn open and closed states
what regulates most channels?
first messengers- extracellular signals, including hormones, neurotransmitters, odorants, air pressure (sound waves), photons (acting on visual cells)
what kind of modulation do ligand-gated channels do?
what do they mediate?
where do they usually operate?
what are 2 examples?
ligand-gated channels (aka ionotropic receptors) do direct modulation by a signaling molecule
mediate r**apid cell-cell communication **
incorporate a channel in a protein that also incudes the receptor, which is usually a hormone or neurotransmitter
when signaling molecule binds receptor, induces a conformational change that opens the channel
present in signaling btwn neurons &transmission from neurons to skeletal muscle cells
eg: cys-loop channels/receptors & glutamate receptors
where do most ligand-gated channels occur?
at a synapse, either btwn neuron-neuron or neuron-muscle cell
what does an **excitatory **stimulus do to a membrane? how do they work?
**depolarizes **the membrane by activating an inward current or reducing an outward current
what does an **excitatory channel **carry?
inward currents
what does an inhibitory stimulus do to the membrane? how?
hyperpolarizes the membrane
increases K+ conductance or activates Cl- conductance
what is hyperpolarization? depolarization?
**hyperpolarization: **if the inside becomes more negative than the outside
**depolarization: **inside becomes less negative than the outside
what is capacitance?
membrane property - the ability to restore charges in the membrane, in response to a current
what is the **effect of capacitance **on Vm?
membrane tends to ignore events that are brief
??
what is the reversal potential?
**reversal potential **of an ion: membrane potential at which there is no net (overall) flow of that particular ion from 1 side of teh membrane to the other
reversal potential = equilibirum potential in a single-ion system
are ligand-gated channels selective for a particular ion?
what’s the effect of this on reversal potential?
b/c they’re ion channels, most aren’t very selective for ions they conduct
therefore, currents that flow thru often are carried by more than 1 ion species
therefore reversal potential for the current is determined by the channel’s relative conductances for the participating ions
what is the structure of Cys-Loop channel receptors?
loop in extracellular N-terminal domain formed by Cys-Cys bridge - where ligand binds to produce conformational chagne in channel
heteromeric or homomeric pentameters (5 subunits)
each subunit has 4 TM spanning helices (M1-4)
large intracellular loop btwn M3-M4 that associates with cytoskeletal partners
walls are formed by five M2 helices
channels are selective for either cations or anions; otherwise, non-discriminating
what are examples of Cys-Loop channels?
1) nAChR, nicotinic acetylcholine receptor
2) GABA-A, gamma-aminobutyric acid receptor
what is significant about the different subunits of a Cys-loop channel?
there are different types of the 5 subunits (alpha-gamma)
depending on if in a muscle cell, neuron in brain, neuron in ANS, will have different complements
**ALL functional channels have at least 2 alpha subunits b/c ACh binds at interface btwn alpha and another subunit **
what is nAChR’s gating model/mechanism? how does it work?
in closed state, kink in M2 helices projects into pore, forming barrier composed of ring of hydrophobic residues
when both M2 are bound by ACh, M2 helices rotate away from center, pore is opened, permits current flow
get very fast channeling through
