Ion Channels Gow 2

Common Characteristics of ALL Ion Channels:

• membrane-spanning ______ forming a barrel

• regulation of ion entry based on ____ and _____ density

• some form of gating mechanism that involves __________ change

• helices

• size charge

• conformational

KAHOOT:

do voltage-gated channels ALWAYS have to undergo conformational change?

YES

KAHOOT:
are NMDA receptors activated by Mg2+ ions or chemicals such asMK-801

NO they are INHIBITED

activated by glutamate or NMDA

KAHOOT:

True or False: Channel opening of ligand-gated channels can only occur with agonist sites occupied

TRUE

ligand must be bound

voltage gated doesn’t need agonist site activated since they are opened by the S4 helix sensing voltage change

KAHOOT:
which muscarinic receptors are inhibitory vs which are agonists?

EVEN = inhibitory (M2 and M4)

ODD = agonist (M1, M2, M3)

which receptor would you want acetylcholine to bind to during times of rest and digest (activate parasympathetic nervous system) ?

M1, M3, M5

ODD ARE AGONSITS

are NMDA or AMPA receptors inhibited by Mg+ and chemicals such as MK-801?

NMDA

KAHOOT:

Kainate, AMPA, and NMDA receptors allow for ____influx ___efflux

Na+ Ca+ influx

K+ efflux

KAHOOT:

TRUE/ FALSE: The two populations of AMPA receptors are potassium and calcium channels.

FALSE

1. Na+

2. Na+ AND Ca2+

NOT POTASSIUM

KAHOOT:

are NMDA and Kainate exctitatory or inhibatory? inhibitory

exctitatory

KAHOOT: Which of the following serotonin receptors acts as an ion channel?

3 (rest rest are GPCR)

KAHOOT: What is the most prevalent ligand-gated channel or receptor in the central nervous system?

why?

GABA bc/ body wants to spend as little ATP as it can and action potentials require ALOT of ATP

KAHOOT:

Do AMPA or NMDA receptors require both glycine and glutamate to bind before allowing Na+ and Ca2+ influx and K+ efflux?

NMDA

which receptor would you want acetylcholine to bind to when you are in danger? (want increase heart rate, blood pressure, decreased pancreatic and salivary liquid)

M2 and M4 since they are INHIBITORY of the parasympathetic (rest and digest) system

KAHOOT:
how many calcium voltage gated subunits exist ?

4

what are 4 types of channel gating?

1. voltage (cross threshold)

2. ligand — can be pH

3. phosphorylation

4. mechanically

what are three types of mechanically gated channels?

1. sheer (endothelial cells)

2. Cilia

3. heat

1. nicotinic acetylcholine receptor

2. seretonin 5-Ht3 recetor

3. Ionotropic Glutamate receptors

4. GABA receptors

the following receptors are ligand gated

once a ligand binds which ions are allowed to pass through each channel?

1. Na+

2. K+

3. Ca2+

4. Cl-

name 4 receptors that are ligand gated:

1. nicotinic acetylcholine receptor

2. seretonin 5-HT3 receptor

3. Ionotropic Glutamate receptor

4. GABA receptor

what opens a voltage gated ion channel ?

the difference in charge between the inside and outside of the cell

ex. if there is more positive charge outisde of the cell

what are three examples of voltaage gated channels that exist?

• Na+ channel

• K+ channel

• Ca2+ channel

how many subunits of 6 helices are there in the sodium channel?

which helices from each subunit form together to create the pore?

which helix from each subunit senses the voltage and allows the pore to open?

4

S5 and S6

S4

how many subunits of 6 helices make up the Ca2+ channel ?

4

how many subunits of 6 helices make up the K+ channel ?

1

only 1 event needed for regulation

the ___ and ___ subunits help in the assembly of the 6 helices

alpha and beta

Calcium in the Synapse:

1. action potentials reach _____ _______

2. ______-gated Ca2+ channels open

3. Ca2+ binds to _____ _____ in cytoplasm

4. Ca2+ + _______ ________ complex stimulate fusion and exocytosis of ____________

• axon terminal

• voltage

• protein sensor

• neurotransmitter

what is the difference between SNARE and SNAP in the axon terminal?

SNARE prepare the vesicles for synaptic fusion DOES NOT CAUSE them to fuse

SNAP initiates SNARE to twist and prepare for fusion and recycles SNARE at end

what are three ways neurotransmitters are turned off?

1. reuptake into presynaptic nerve

2. diffusion (removal by other cells - glia)

3. enzymatic degradation (ex. acetylcholine esterase)

Calcium in the Muscle:

_____________ provides the trigger at the motor end plate leading to DEPOLARIZATION

activation of ___-type calcium channels lead to calcium-mediated calcium release

intracellular _______ activates the contractile machinery

signal is turned off by _____ degradation and ______ reuptake

• acetylcholine

• L

• calcium

• acytelcholine degradation + calcium reuptake acetylcholine

Caclium in the Muscle:

1. acetylcholine binds to which receptor allowing Na2+ to come in and propogate the action potential to the t-tububles

2. what does the depolarization of the muscle cell lead to?

3. how does the sarcoplasmic reticulum respond to extracellular calcium?

4. ultimately what is the role of calcium in muscle contraction?

5. what happens once calcium has done its job and excess is no longer needed?

• Nicrotinic (NaCHr)

• opening of L-type CA2+ channels to led extracellular Ca2+ to come into the muscle

• extracellular Ca2+ triggers the release of more calcium from the sarcoplasmic reticulum through ryanodine receptors

• bind to troponin on actin allowing myosin head to bind to actin

• calcium reuptake by the sarcoplasmic reticulum

________ cells are modified neurons

what stimulates the change in membrane potential?

what is an example?

• neuroendocrine

• adrenal medulla

• chromaffin cell of the adrenal gland

what is calcium’s role in the neuroendocrine system?

calcium leads to vesicle fusion and triggers the release of hormones to the blood stream

drugs can mimic (agonize) or block (antagonize) ___________ ligands that regulate the flow of ions through channels in the plasma membrane

endogenous

what are examples of natural ligands that open ion channels (synaptic transmitters) that can be blocked or mimicked by drugs

acetylcholine (parasympathetic + muscle)

serotonin (regional regulator)

GABA (block action potential)

glutamate (stimulate action potential)

where can acetylcholine be found?

• neuromuscular junction (motor neuron —> muscle)

• autonomic ganglia of the CNS

• postganglionic parasympathetic nerve- target organ junctions

• brain

acetylcholine can stimulate target organs via _________ neurons such as the _________ nerve (parasympathetic)

cholinergic

VAGUS

cholinergic activity causes

• ________________ of blood vessels

• increases fluid secretion from ________ and ______ _______

• ___________ heart rate

• dilation

• pancreas salivary gland

• slows

are the nicotinic or muscarinic receptors metabotropic (GPCR)?

muscarinic

which acetylcholine receptor is ligand gated?

nicotinic

what happens when acetylcholine binds to a nicotinic receptor ?

increase Na+ and K+

what happens when acetylcholine binds to muscarinic 1, 3, or 5 receptors?

are its effects stimulatory or inhibitory?

increase IP3 and DAG

increase Ca2+

stimulatory

what happens when acetylcholine binds to muscarinic 2 or 4 receptors?

are its effects stimulatory or inhibitory?

decrease cAMP

increase K+ (since increase leaky K most likely to repolarize— less likely to fire)

inhibitory

stimulation of which acetylcholine receptor leads to nerve DEpolarizaition and muscle contractions?

nicotinic (nAChR)

many nicotinic cholinergic receptors in the brain are located PRESYNAPTICALLY on ____ ________ and they facilitate the release of this transmitter

axon terminals

what is the difference between an Nm and Nn nicotinic receptor?

Nm = muscle receives a signal from the nerve

Nn= nerve receives a signal from another nerve

if nicotine were to bind to a nAChR instead of acetylcholine, what would happen?

mimic effects so muscle contraction + nerve depolatization

_____________ is the main EXCITATORY neurotransmitter in the brain and spinal cord

______ is the main INHIBITORY neurotransmitter in the brain

Glutamine

GABA

how is glutamine converted to glutamate ?

hydrolysis reaction catalyzed by glutaminase

NH2 group removed from glutamine and replaced with OH and the other H of H20 binds with NH2 to make NH3

left with glutamate + NH3

which enzyme catalyzes the following hydrolysis reaction

Glutamine + H20 —→ Glutamate + NH3

glutaminase

how to you get from glutamine to glutamate to GABA?

glutamine undergo hydrolysis to get glutamate and decarboxylation to get to GABA

which enzyme and coenzyme catalyzes the following hydrolysis reaction

Glutamate —→ GABA + CO2

enzyme: glutamate decarboxylase

coenzyme: PLP (prosthetic group)

which enzyme and coenzyme is involved in the conversion of glutamate to alpha keto glutarate?

what type of reaction takes place?

enzyme: glutamate dehydrogenase

coenzyme: NAD+ —> NADH

oxidative deamination

glutamate + NAD+ + _______

—→ a-ketoglutarate +NADH

H2O (mediator for unstable intermediates)

does glutamate bind to metabotropic or ionotropic receptors ?

BOTH

what happens to IP3, DAG, and cyclic AMP levels when glutamate binds to metabotropic receptors?

increased IP3 and DAG

decreased cyclic AMP

what are the most potent glutamate and GABA receptors?

are these receptors ionotropic or metabotropic?

1. AMPA Kainate (Glutamate)

2. NMDA (glutamate)

3. GABA a (GABA)

all three are ionotropic

which two glutamate receptors increase Na+, K+ , and Ca2+ channels

are they ion channels or GPCRs?

AMPA Kainate + NMDA

ion channels

which GABA receptor allows Cl- into the cell causing repolarization terminating the action potential?

is this receptor ionotropic or metabotropic?

GABA a

ionotropic

which GABA receptor is a GPCR ?

does it increase of decrease on IP3 and DAG ?

how does it impact K+ and Ca2+

GABA b

increase IP3 and DAG

decrease Ca2+ increase K+ leaky channels

AMPA and Kinate are IONOTROPIC ________ receptors

glutamate

Kainate Receptors (glutamate receptor):

Kainate is an ______ isolated from RED ALGAE SEEWEED

Ion channel that allows for Na+ ______ and K+ ___

May play a role in _______ transduction (epilepsy?) and synaptic ________

• acid

• influx efflux

• sensory plasticity

AMPA (gutamate receptor):

• there are TWO populations of AMPA receptors

  • one only allows for ____ influx

  • the other allows for both ____ AND _____ influx

• AMPA is an artificial ______ analog

• important for _____ synaptic transmission (doesn’t START firing itself)

Na+

Na+ AND Ca2+

glutamate

fast

when _______ and glutamate (BOTH MUST BIND) bind to NMDA the open channel opens

NMDA receptor is a _____ channel

• influx of

• efflux fo

NMDA is a _______ AGONIST

glycine

Na+ AND Ca2+

K+

selective

how are NMDA receptors inhibited?

Magnesium (Mg+) or chemicals such as MK-801

once glutamate AND glycine bind to NMDA Na+ and Ca2+ come into the cell and K+ leaves the cell

what overall effect does this have

strengthening synaptic plasticity and memory

the GABA ____ receptor is a chloride ion channel

• different combinations of 15+ subunits are used to create the ____ subunit pore for the receptor

  • 2 out of the ___ subunits are ALWAYS _______

• a

• 5

• 5 alpha

allosteric site of GABA increase/ decrease infinity for GABA

increase

5-hydroxytryptamine, 5-HT

• what are the TWO ways serotonin is removed from the synaptic cleft?

• reuptake (SSRI inhibit reuptake to keep in synaptic cleft longer and extend effect)

• monoamine oxidase inactive seretonin (MAO)

what is the inactivated form of serotonin ?

what causes this inactivation?

5-Hydroxy indoleacetic acid (5-HIAA)

monoamine oxidase

how would increased levels of MAOIs impact serotonin?

increase seretonin

monoamine oxidase converts seretonin to inactivated 5-HIAA so if you inhibit them then seretonin increases

which serotonin receptor is the ONLY ion channel (the rest of GPCR)

which ion channel is opened?

5-HT 3

Na+

which serotonin receptors decrease second messenger cyclic cAMP

1A

1B

1D

Even though 5-HT 1A, 1B and 1D all decrease cAMP what stands out about 5-HT 1D?

1A and 1B increases K+ channels while

1D DECREASES K+ channels

which 5HT receptors increase IP3 and DAG ?

what effect does this have on K+ channels?

2A and 2C

decrease K+ channels

which 5HT receptor INCREASE cyclic AMP?

4

which 5HT receptor INCREASE cyclic AMP?

which 5HT receptor DECREASE cyclic AMP?

increase = 4

decrease = 1a, 1b, 1d (decrease K+ channel)

which two serotonin receptors decrease k+ efflux ?

• 1D (decrease cAMP BUT still decrease K+ channels)

• 4 (increase cAMP so decrease K+ hyperpolarizing channels)

• 2A (Increase IP3 and DAG decrease hyperpolarizing K+ channels)

• 2C (Increase IP3 and DAG decrease hyperpolarizing K+ channels)

which receptors increase K+ efflux (increase K+ leaky channels) and which decrease K+ efflux

increase = 1A, 1B

decrease= 1D, 4, 2A, 2C