NEUS 609 - Neurotransmitters & their Receptors

ionotropic receptors

• aka ligand-gated ion channels

• NT binding results in opening or closing of ion channels

• FAST but SHORT-LIVED effects

• activation is often followed by a desensitization period

• allow inflow OR outflow of ions

• causes changes in membrane potential supporting or inhibiting activity

metabotropic receptors

• aka G-protein coupled receptors

• also ligand gated but exert effects via changes in intracellular signaling

• INDIRECT

• SLOW but LONG-LASTING effects

• require second messengers

• signal amplification

• can affect gene expression and mRNA

4, ion pore, intracellular loop

ionotropic receptors are made of subunits, each made of __ transmembrane domains, which arrange themselves around an ___.

They often have an ___ which shifts receptor to active/desensitized/inactive states.

homomeric

all subunits making up the ionotropic receptor are the same type.

heteromeric

ionotropic receptor is made of ___ subunit(s)

permeability, concentration gradients

ionotropic receptors activity depends on:

1. ___ to either anions or cations

2. the ___ of these specific ions

size, charge

the specificity/selectivity of ligand-gated ion channels is due to the __ and __ of the inside of the channels.

chloride

inhibitory NTs bind to receptors causing an influx of __ ions

sodium, calcium

excitatory NTs bind to ligand-gated ion channels that allow and influx of ___ or ___

hyperpolarization

making the inside of the cell more negative

depolarization

making the inside of the cell LESS negative/more positive

transport pumps

membrane potential is maintained at -70mV by potassium ____ which cause a K+ EFFLUX

excitatory postsynaptic potential

aka EPSP

cation INFLUX or anion EFFLUX

inhibitory postsynaptic potential

ka IPSP

cation EFFLUX or anion INLFUX

fast neurotransmission

___ is mediated by rapid changes in membrane electrical potential through ligand-gated ion channels which are determined by electrochemical gradients

activity-independent release

• found at axo-axonic synapses

• NT release in absence of action potential

• usually recorded as MEPSPs

• ligand-gated axo-axonic synapses can transmit signal from another neuron

superfamilies of ionotropic receptors

• cys-loop

• ATP-gated channels

• Glutamatergic cation channels

Cys-loop superfamily

• has 5 subunits

• nicotinic cholinergic cation channels

• GABAa & GABAc anion channels

• Glycine anion channels

• 5-HT3 cation channels (serotonin)

ATP-gated channels superfamily

• has 3 subunits

• usually found in organelles

• P2X

Glutamatergic cation channels superfamily

• has 4 subunits

• NMDA

• AMPA

• Kainate

within

alpha, beta, delta, epsilon, gamma are subunits __ each neurotransmitter family

• different between all neurotransmitter families

subunit, 7, 3

for metabotropic receptors, 1 __ = 1 receptor and each receptor has __ transmembrane domains.

• each receptor is associated to a G-protein, and each G-protein is made of __ subunits

intracellular

metabotropic receptors function by activating ___ enzyme systems to produce an ___ signal which is called the second messenger

GTP

when bound to ___ the G-protein is ACTIVE

• when active, the alpha subunit of G-protein relocates to activate an enzyme/protein

GDP

when bound to ___ the G-protein is INACTIVE

G protein

guanine nucleotide protein transmitting chemical messages from outside the cell into intracellular changes in signaling

Second messenger

substance activated or inhibited by G-protein that initiates activity in a cell

Gi, Go

inhibitory because decrease adenylyl cyclase activity

• decrease cAMP levels

• decease PKA activity

increase K+ channels activity aka K+ conductance

Gs, Goff

excitatory because increase adenylyl cyclase activity

• increase cAMP levels

• increase PKA activity

Gq

excitatory because it increases phospholipase C activity, which cleave compound into IP3 which release Ca2+ into cytosol, and into DAG which increases PKC activity

guanine exchange factors

GPCR act as ___ aka GEF for heteromeric G-protein.

non-covalent catalysts

GPCRs act as ___ as G-proteins dissociate from receptors and stimulate other proteins which in turn stimulate second messenger molecules

signal amplification

metabotropic receptors experience ___ because the intracellular signaling cascade continue for a bit even after the receptor is deactivated.

classical NTs

• amino acids (GLU, GABA, Glycine)

• Acetylcholine (ACh)

• Monoamines (DA, NE, E, Serotonin)

Nonclassical NTs

• neuropeptides (endorphins, enkephalins)

• Lipids (endocannabinoids)

• Gases (nitric oxide NO)

Conditions to be a NT

• contained in presynaptic cell

• can be inactivated

• released from axon terminal upon stimulation

• postsynaptic receptors for it

• agonist drugs have same effect on postsynaptic receptors

• antagonist drugs have opposite effects on postsynaptic receptors

V-ATPases

small molecule NTs are packed into vesicles at high concentrations against their concentration gradients via ___ aka vesicular proton pumps