Electro-neutral ionic transport

Description

Neuronal ionic co-transporters NKCC1 and KCC2 are two neuronal co-transporters involved in Cl homeostasis and cell volume regulation. Dysfunction of these two co-transporters has consequences on neuronal excitability leading, in extreme cases, to pathogenesis of seizures and chronic neuropathic pain. The fact that NKCC1 and KCC2 co-transport have electro-neutral positive and negative charges makes the study by electrophysiology impossible.

Material and methods

  • Biological Model: Primary cultures of cortical neurons prepared from E17 OF1 mice embryos of either sex
  • DHM® solution: Non-invasive optical recording of neutral ionic co-transporters.

Results

DHM® is the first imaging technique offering the possibility to dynamically and directly monitor the activities of the two neuronal co-transporters NKCC1 and KCC2 in situ. Moreover, DHM® provides the possibility to pharmacologically characterize NKCC1 and KCC2. This is based on the fact that NKCC1 and KCC2 co-transport ions and water (up to 600 water molecule by charge), an underlying phenomenon which can be optical recorded by DHM®.

Figure 6 (adapted from Jourdain et al., J. Neurosc., 2011)

Publications

Jourdain et al., J. Neurosc., 2011

1: Biphasic response triggered by glutamate (30 µM, 30s, arrow head) in control condition (red line) and in the presence of furosemide (Furo., 100 µM, blueline). 2: RD response triggered by glutamate (30VM, 30s, arrow head) in control condition (red line) and in the presence of furosemide (blue line). 3: Concentration response curves of the inhibitory effect of furosemide on biphasic (full square and full line; IC50 = 580nM) and RD (empty square and dotted line; IC50 = 550nM) respons