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DA Transporter Currents: A Reason for Excitement. Susan L. Ingram WSU-Vancouver, Vancouver WA. Neurotransmitter transporters: Transport is electrogenic. Neurotransmitter. DA, 5HT, NE, GABA, Glycine . +. 1. -. 3 Na. -. 1Cl. Substrate-gated uncoupled conductance. cytoplasm.

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da transporter currents a reason for excitement

DA Transporter Currents: AReason for Excitement

Susan L. Ingram

WSU-Vancouver, Vancouver WA

slide2

Neurotransmitter transporters: Transport is electrogenic

Neurotransmitter

DA, 5HT, NE, GABA, Glycine

+

1

-

3Na

-

1Cl

Substrate-gated

uncoupled conductance

cytoplasm

extracellular

space

questions
Questions
  • Does activation of DAT produce measurable currents in DA neurons?
  • What ions are responsible?
  • Is the current large enough to change excitability of the DA neurons?
  • Does the current play a role in neurotransmitter release?
slide4

Presynaptic

cell

MGluR

GIRK

D2

X

X

Amph

COC

D2

D1

a1

Postsynaptic

cell

Dopaminergic Synapse

DA

DA

dat currents are uncoupled from transport

50

Current (pA)

10-9

10-9

10-5

10-5

[DA]

0.1

Uptake (fmol/cell/s)

[DA]

DAT currents are uncoupled from transport
slide10

DAT currents are carried by chloride ions

control

nitrate

Normalized current

Voltage (mV)

-100

pNO3/pCl = 14

* Permeability to nitrate is 10-fold greater than

GABAA-mediated chloride conductance (pNO3/pCl = 2.5)

da stimulates firing by a d2 independent mechanism
DA stimulates firing by a D2-independent mechanism

* Shi, et al. (2000) Dual effects of amphetamine on dopamine neurons mediated by

dopamine and nondopamine receptors. J Neurosci 20(9):3504-3511.

slide15

Muscimol - control

DA - control

Vrest

Vrest

Normalized current

Normalized current

Voltage (mV)

Voltage (mV)

GABAA-mediated chloride conductance is inhibitory

* Gramicidin perforated-patch recordings

DAT-mediated chloride conductance is excitatory

slide17

Is the DAT-mediated excitation sufficient

to stimulate neurotransmitter release?

slide22

Conclusions

  • DAT mediates an uncoupled chloride conductance.
  • DAT currents in neurons are activated at much lower DA concentrations than the D2-receptor or transport.
  • The DAT-mediated chloride conductance excites DA neurons.
  • Activation of DAT-mediated currents is a potential
  • mechanism for stimulating DA release in the SN.
slide23

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