L3 - Transporters Flashcards by megan falco

define passive diffusion

movement of molecules from region of high concentration to low concentration across a membrane

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what type of molecules can passively diffuse? give examples

small
uncharged
non polar
lipid soluble

O2, CO2, glycerol, ethanol

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fucntion of transmembrane proteins

form transporters or ion channels that allow movement of large / polar molecules across membrane

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function of ion channels

act like a pore to allow passive diffusion of specific ions through the membrane

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define facilitated diffusion

passive diffusion of molecules facilitated by a protein eg ion channel

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define primary active transport

using a carrier protein (transporter) and energy provided from conversion of ATP to ADP +Pi (via ATPase) to transport a molecule across a membrane against its conc gradient

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example of primary active transporter

Na / K / ATPase pump

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define secondary active transport

uses energy from the flow of ions down a concentration gradient to co-transport another molecule against its conc gradient across a membrane

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what are the two types of secondary active transport

symport (cotransport) -> molecule transported in same direction as ion providing the energy

antiport -> molecule transported in opposite direction to ion providing the energy

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list the 3 functional types of transporter

transporters that maintain ion gradients (ion transporters and pumps)
nutrient / metabolite transporters
NT transporters

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why is NT re-uptake from the synaptic cleft important?

prevent new unwanted AP generation

- synapse would become refractory/inactivated due to receptor desensitisation if NT wasnt removed

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how are NT removed from cleft

passive diffusion into surrounding neurones
degradation by enymes
reuptake into terminal or astrocytes

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what are the two types of plasma membrane transporter superfamilies

Na+ / Cl- dependant transporters

2. Na+ /K+ dependant transporters

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how many TMDs do the Na+ / Cl- dependant transporters have

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are the N and C terimnals of the Na+ / Cl- dependant transporter intra/extra cellular?

both intracellular

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describe structure of Na+ / Cl- dependant transporter superfamily

→ 12 transmembrane (H.phobic) domains

→ intracellular N & C terminal

→ extracellular loop between TMD 3&4 which contains 2-4 glycosylation sites

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give examples of transporters that are Na+ / Cl- dependant

SERT
NET
DAT
GABA transporter
Glycine transporter
choline transporter

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list the types of glutamate transporters

EAAT 1-5

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where is 
EAAT1 
EAAT2 
EAAT3
EAAT4
EAAT5
found

EAAT1 -> glial cells
EAAT2 -> glial and neuronal cells
EAAT3 &4 -> neuronal cells
EAAT5 -> retina

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how many TMDs do the Na+/K+ dependant transporters have

6-10 Hphobic

example of a Na+/K+ dependant transporter

EAAT (glutamate and aspartate transporter)

what is an electroneutral transporter and give an example

a transporter that doesnt change the electrochemical portetial of a cell (moves same number of + / - in and out)

SERT

what is an electrogenic transporter and give an example

a transporter that changed the electrochemical potential of a cell (moves an odd number of + / - in or out of the cell)
glutamate EAAT

where else is EAAT3 expressed other than glutamate neurones and why

GABAergic neurones as glutamate is the precursor for GABA

why is glutamate re-uptake into glial cells more energy efficient?

requires less energy because there is a smaller concentration gradient of Glutamate in the glial cell compared to the nerve terminal due to conversion of glutamate to glutamine in glial cells

describe the glutamate - glutamine shuttle process

1. glutamate taken into glial cell by EATT1/2 where its converted to glutamine by glutamine synthase 2. glutamine leaves glial cell via N amino acid transporter 3. glutamine transported into neurone by A amino acid transporter 4. glutaminase converts glutamine back into glutamate in the nerve terminal 5. glutamate packaged into vesicle

what ion is used to co transport in the A and N amino acid transprters?

describe calcium independant NT release

reverse transport -> when transporters work in reverse and move NT into the cleft rather than into nerve terminal

what enzymes convert glutamate -> glutamine glutamine -> glutamate

glutamine synthase | glutaminase

what GABA transporters are found on the membranes of astrocytes

GAT-2 | GAT-3

what is believed to cause reverse transport of NTs?

the Na gradient that usually co-transports the NT in. if intracellular Na gets too high it may move in the opposite direction into the cleft (via the transporter) taking NT with it

what does packaging NT into vesicles prevent

- leakage into cleft - NT metabolism in the terminal - toxicity to neurone

``` name the monoamine ACh GABA/Glycine Glutamate transporters ```

VMAT (1&2) VAchT VIAAT (vesicular inhibitory amino acid transporter) V-glut 1, 2, 3

what does VMAT transport

serotonin dopamine NA histamine

what does VMAT transport

serotonin dopamine NA histamine

where is VMAT1 VMAT2 expressed

endocrine cells | neurones

what is a difference between the vesicular and plasma membrane glutamate transporters?

the membrane transporter transports aspartate and glutamate, the vesicular can only transport glutamate

describe structure of the VMAT and VAchT transporters

- 12 TMDs - large Hphilic loop with 3-5 potential glycosylation sites between TMD 1&2 (in vesicle lumen) - N and C terminal is in cytoplasm of nerve terminal

describe structure of VIAAT

- 10 TMDs - Long N terminal and short C terminal, both in cytoplasm of nerve terminal - large loop between TMD 1&2 (inside vesicle)

describe significance of glutamate transporters in epilepsy

- knockout mice for the equivalent EAAT2 transporter experienced seizures

name the GABA plasma membrane transporter

GAT

describe the mechanism of anti-epileptic drug tiagibine

1. it is a GABA transporter blocker - prevents re-uptake of GABA into nerve terminal 2. increases [GABA] in cleft and so increases receptor binding 3. increased inhibition

list diseases that can be treated by interfering with transporters (and which transporters)

1. Epilepsy -> GAT blockers 2. ADHD -> DAT blockers 3. Depression -> NA / 5-HT (NET / SERT) blockers

describe the mechanism of action of fenfluramine (anti-obesity drug) in regards to the serotonin transporter

causes SERT to work in reverse, depositing 5-HT into the cleft instead of re-uptaking it (reverse transport) also disrupts vesicle storage

wwhat effect will blocking VMAT and other vesicle transporters have?

reduce [NT] in the cleft, as less can be exocytosed

describe significance of reverse transport in ischemia

reverse tsport of plasma membrane glutamate transporters occurs in ischemia, which results in increased [glutamate] in cleft causing excitotoxicty

where does cocaine act?

SERT, DAT, NET | inhibiting reuptake

where does amphetamine act?

DAT, SERT, NET clocking reuptake also causes DAT reverse transport

where does MDMA act?

SERT, where it blocks reuptake and promotes reverse transport MDMA has higher affinity for SERT than serotonin itself