Exam 2: Ligand gated ion channels

what are ionotropic receptors?

Membrane bound proteins that have an ion permeable core

What makes up an ionotropic receptor?

5 domains, with each domain containing 4 membrane spanning subunits-the amino acids determine the function. Nicotinic acetylcholine receptors are model ionotropic receptor for studying these types.

describe the pore of the nicotinic acetylcholine receptor

the pore has negatively charged amino acids, which makes the channel selective for cations over anions. Based on the A.A that line the pore and how narrow it is, that will determine if monovalent ions (+1 charge) or divalent ions (+2 charge) can get through.

What opens the nicotinic acetylcholine receptor?

2 ACh must bind to cause a conformational change in the channel and open the receptor. ACh enters pore to have access to the binding sites, and the binding of the first ACh makes binding of the second more favorable. Once both are bound, the conformational change occurs and open central pore to let ions through.

What post translational modifications do ionotropic receptors go through?

Phosphorylation of receptor by kinases on cytoplasmic side. Occurs to desensitize channels after opening, meaning opening of channel is less likely.

Why are glutamate ionotropic receptors unique?

They have NMDA, AMPA and Kainate as glutamate binding receptors, only have one unit that does not span the membrane entirely (TMZ), the pore non selectively lets in cations depending on which subunit is present. NMDA receptors allow calcium to flow in.

What does mRNA splicing of GluRs do?

produces different channels, calcium permeability and sensitization rates will change.

What are the two features of glutamate transmission via NMDA receptors?

there is a magnesium block that requires the membrane to be depolarized to be removed, the receptor is especially permeable to calcium

What is glutamate exitotoxicity?

it is common following injury or stroke, results bc of excessive calcium that causes glutamate release that then lets in calcium. Calcium activates variety of secondary pathways that kill or damage neurons.

What is PCP?

pore blocker of the NMDA receptor