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.
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)
The passive or active transport of water through a plasma membrane is a concomitant of several cellular processes. Even if the functional involvement of water channels, called aquaporin, is known for two decades, the trans-membrane water movements during cellular processes remain largely unknown. One of the reasons why this area is still under-explored is due to the lack of reliable measurement techniques to directly quantify the trans-membrane water fluxes, at cellular scale, during a physiological (and pathological) situation.
DHM® is the only imaging technique able to monitor in situ net fluxes of water during a cell process (osmotic shock, functional coupling between the epithelial chloride channel CFTR and the aquaporin AQP3). These results open the field for new types of pharmacological investigations (notably the screening of drugs acting on water transporter molecules) and therapeutic approaches.
Figure 5 (adapted from Jourdain et al., JCS, 2014)