Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus

M. A. Belenky, P. J. Sollars, D. B. Mount, S. L. Alper, Y. Yarom, G. E. Pickard

Research output: Contribution to journalArticle

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Abstract

The suprachiasmatic nucleus (SCN) is a circadian oscillator and biological clock. Cell-to-cell communication is important for synchronization among SCN neuronal oscillators and the great majority of SCN neurons use GABA as a neurotransmitter, the principal inhibitory neurotransmitter in the adult CNS. Acting via the ionotropic GABAA receptor, a chloride ion channel, GABA typically evokes inhibitory responses in neurons via Cl- influx. Within the SCN GABA evokes both inhibitory and excitatory responses although the mechanism underlying GABA-evoked excitation in the SCN is unknown. GABA-evoked depolarization in immature neurons in several regions of the brain is a function of intracellular chloride concentration, regulated largely by the cation-chloride cotransporters NKCC1 (sodium/potassium/chloride cotransporter for chloride entry) and KCC1-4 (potassium/chloride cotransporters for chloride egress). It is well established that changes in the expression of the cation-chloride cotransporters through development determines the polarity of the response to GABA. To understand the mechanisms underlying GABA-evoked excitation in the SCN, we examined the SCN expression of cation-chloride cotransporters. Previously we reported that the K+/Cl- cotransporter KCC2, a neuron-specific chloride extruder conferring GABA's more typical inhibitory effects, is expressed exclusively in vasoactive intestinal peptide (VIP) and gastrin-releasing peptide (GRP) neurons in the SCN. Here we report that the K+/Cl- cotransporter isoforms KCC4 and KCC3 are expressed solely in vasopressin (VP) neurons in the rat SCN whereas KCC1 is expressed in VIP neurons, similar to KCC2. NKCC1 is expressed in VIP, GRP and VP neurons in the SCN as is WNK3, a chloride-sensitive neuron-specific with no serine-threonine kinase which modulates intracellular chloride concentration via opposing actions on NKCC and KCC cotransporters. The heterogeneous distribution of cation-chloride cotransporters in the SCN suggests that Cl- levels are differentially regulated within VIP/GRP and VP neurons. We suggest that GABA's excitatory action is more likely to be evoked in VP neurons that express KCC4.

Original languageEnglish (US)
Pages (from-to)1519-1537
Number of pages19
JournalNeuroscience
Volume165
Issue number4
DOIs
StatePublished - Feb 17 2010

Fingerprint

Suprachiasmatic Nucleus
Chlorides
gamma-Aminobutyric Acid
Neurons
Vasoactive Intestinal Peptide
Gastrin-Releasing Peptide
Vasopressins
Cations
Neurotransmitter Agents
Member 2 Solute Carrier Family 12
Sodium-Potassium-Chloride Symporters
Body Patterning
Biological Clocks
GABAergic Neurons
Circadian Clocks
Chloride Channels
Protein-Serine-Threonine Kinases
GABA-A Receptors
Cell Communication
Protein Isoforms

Keywords

  • GABA
  • KCC2
  • KCC4
  • NKCC1
  • WNK3
  • circadian rhythms

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus. / Belenky, M. A.; Sollars, P. J.; Mount, D. B.; Alper, S. L.; Yarom, Y.; Pickard, G. E.

In: Neuroscience, Vol. 165, No. 4, 17.02.2010, p. 1519-1537.

Research output: Contribution to journalArticle

Belenky, M. A. ; Sollars, P. J. ; Mount, D. B. ; Alper, S. L. ; Yarom, Y. ; Pickard, G. E. / Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus. In: Neuroscience. 2010 ; Vol. 165, No. 4. pp. 1519-1537.
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