Neurotransmitter Receptors

You can have ________ types of receptors for the same NT.

multiple

ACh is _________ to the heart muscle, but is ________ to skeletal muscle.

inhibitory; excitatory

ACh receptors at the heart are ___________ and not nicotinic.

muscarinic

______________ alone mimics the effects of ACh. (muscarinic receptor)

Muscarine

__________ blocks the effects of ACh (muscarinic receptor)

Atropine

__________ alone has no influence on the heart (muscarinic receptor)

Nicotine

__________ does not block effects of ACh on heart (muscarinic receptor), the heart will obey ACh (slow down)

Curare

If we put ACh on, what will it do to either of those receptors? (nicotininc and muscarinic)

activate both

When nicotine binds to the nicotinic receptor, it?

opens the channel

When nicotine is near the muscarinic receptor, it?

cannot bind (nothing happens)

When muscarine is near the nicotinic receptor, it?

cannot bind

When muscarine binds to the muscarinic receptor, it?

opens the channel

Are nicotinic receptors ligand gated or G-protein coupled receptors?

ligand gated

Are muscarinic receptors ligand gated or G-protein coupled receptors?

G protein coupled receptors

What do ligand channels allow to pass through the membrane?

positive charges (Na and K)

What does the beta-gamma subunit of muscarinic receptors open?

K channels

How does K slowdown the heart rate?

by hyperpolarizing the membrane potential

What is the agonist for nicotinic receptor?

nicotine

What is the agonist for muscarinic receptor?

muscarine

What is the antagonist for nicotinic receptor?

curare

What is the antagonist for muscarinic receptor?

atropine

What type of receptor is a muscarinic receptor?

metabotropic receptor

What is the main excitatory neurotransmitter?

glutamate

What is the main inhibitory neurotransmitter?

GABA (or glycine)

The muscarinic receptor is an ___________ receptor.

ACh

What do antagonists do in the binding pocket?

they block NTs

Both main classes of receptors are ___________ proteins.

transmembrane

What is the primary mechanism of glutamate?

ligand gated ion channel

What is the primary mechanism of GABA?

chloride ligand gated ion channel

GABA and glutamate use both _________ and __________.

ligand gated; GPCRs

Metabotropic receptors are also known as?

G protein coupled receptors (GPCRs)

What is the reversal potential?

when the net current is zero

If you have only one ion moving, the reversal for it is going to be _______ to the ion’s equilibrium potential.

equivalent

When ACh binds the ligand gated receptor, the gate opens, ___ ions move in, and ___ ions move out, and then the ligand will unbind and the receptor will close.

Na; K

If we voltage clamp the membrane at K+ equilibrium potential, what will happen to the flow of ions?

K will not move, massive Na influx

What does negative current represent?

positive ions flowing into the cell

Why do we get a large Na influx when the cell’s membrane potential matches K?

because we are far from Na equilibrium potential (large driving force)

During reversal potential, the ions are equally ________ each other out/

canceling

When the current has reversed, the amount of K+ leaving the cell is _______ than the Na+ entering the cell.

larger

When less K+ is leaving the cell than the Na+ is entering, the current is _________.

negative

If the reversal potential lands right on E_K, what does that tell you?

membrane is only permeable to K

What is the equation for current (I)?

I = g * (V_M - E_ion)

What is conductance in graphical terms?

the slope of the line

How do you increase conductance?

add more receptors

If the reversal potential does not lie on any one equilibrium potential, what does it suggest?

that more than one ion is moving

What does it mean if more than one ion is moving?

it is a nonselective cation channel

What stops some cations from flowing through the channel?

size (ex Mg is too big)

The end-plate potential peaks at the _________ __________. (the potential at which the inward Na and outward K currents are equal)

reversal potential

The end-plate potential is the _______ in membrane potential caused by the currents that flow into the muscle.

change

Why do the end-plate potential graphs go back down after peaking?

represents the receptors closing

Ionotropic receptors directly allow what?

flow of ions through channels

How do larger molecules exert their effects on the cell when they can’t fit through the cell membrane?

via second messengers

What are some examples of first messengers?

hormones, drugs, NTs

What are some examples of second messengers?

cyclic nucleotides, ions, phospholipids

Metabotropic receptors have a __________ role and primarily modify or adjust the ___________ response to standard ionotropic activity.

modulatory; postsynaptic

Metabotropic responses are ______ and _______, compared to ionotropic receptors.

slow; long

GPCRs are ________ associated with the membrane.

tightly

GPCRs are what?

heterotrimeric (3 subunits)

What does the alpha subunit do in a GPCR?

binds guanine nucleotides and is the major mediator of the G protein actions

What is an effector?

protein/enzyme that is activated/inhibited by a G protein to carry out the actually cellular response

What does the beta-gamma dimer do in a GPCR?

supports the interactions of the alpha subunit with the plasma membrane, but can also regulate effectors

Alpha subunit =

second messengers

Beta-gamma subunit =

direct effects

GPCR contains 7 _______ _________.

transmembrane domains

NTs bind on the ______________ side.

extracellular

G-proteins bind on the ____________ side.

intracellular

NT binding likely _________ the receptor so it can efficiently bind the G-protein trimer.

stabilizes

What is the G-protein receptor activation cycle?

1) ligand binds and G-protein associated with receptor

2) GDP is exchanged for GTP on the alpha subunit

3) alpha and beta-gamma subunits dissociate from each other

4) ligand unbinds from receptor

5) alpha subunit hydrolyzes GTP to GDP

6) alpha and beta-gamma subunits reassociate

What are the 3 types of G proteins?

GS, GI, GQ

GS proteins are ________ proteins.

stimulatory

What does the GS protein activate?

adenylyl cyclase

What does adenylyl cyclase do?

takes ATP and catalyzes the synthesis of cAMP

What does cAMP do?

activates cAMP dependent protein kinases (ex PKA) which can phosphorylate other things

What are the steps of GS stimulation?

1) activate adenylyl cyclase

2) catalyze synthesis of cAMP

3) activate cAMP dependent protein kinases

Gi proteins are ________.

inhibitory

What does the Gi protein inhibit?

adenylyl cyclase

The Gi protein can also exert ______ effects.

direct

Gi proteins activate what?

K channels

In Gi proteins, the beta-gamma subunit binds to ___ channels, opening them.

K+

What happens when Gi opens the K channels?

K flows out of the cell (hyperpolarization)

Gq proteins activate what?

phospholipase C (PLC)

What does PLC do?

converts PIP₂ into IP₃ and DAG

What does IP₃ do?

releases Ca from the ER

What does DAG do?

activates PKC

What are the ways to terminate the G protein cascade?

1) g-protein self inactivation

2) cAMP breakdown and kinase inactivation

3) receptor restoration

4) channel dephosphorylation

What is G-protein self inactivation?

alpha subunit hydrolyzes GTP back to GDP (cascade termination method)

What is cAMP breakdown and kinase inactivation?

phosphodiesterase enzymes convert active cAMP into inactive 5’ AMP (cascade termination method)

What is receptor restoration?

NT detaches from receptor allowing alpha subunit to reassociate with beta-gamma subunit (cascade termination method)

What is channel dephosphorylation?

phosphatases away phosphates from ion channels and return them to their pre-activated state (cascade termination method)

What are the most common G proteins?

Gs and Gi

Some G proteins have very limited distribution for _______ functions. (ex Gt being limited to the photoreceptors)

specific

What are advantages to second messenger signaling?

amplification, persistent response, and regulation

GPCR activation leads to __ _______ activation.

G protein