Abstract
BackgroundDuring development the switch from a depolarizing to a hyperpolarizing action of GABA is a consequence of a decrease of the Na+-K+-2Cl- co-transporter (NKCC1, Cl--uptake) and increase of the K+-Cl- co-transporter (KCC2, Cl--extrusion) expression. However albino visual cortex neurons don't show a corresponding decrease in intracellular chloride concentration during development of the visual system as compared to pigmented animals.ResultsOur study revealed that more cells express NKCC1 in albinos compared to pigmented rat visual cortex neurons whereas KCC2 is expressed in all cells in both strains. We determined a positive relationship between the presence of NKCC1 and an inhibitory deficit in single neurons of the albino visual cortex. After pharmacological blockade of NKCC1 function with its specific inhibitor, bumetanide, the reversal potential of electrically evoked GABAA receptor-mediated postsynaptic currents and, as a consequence, [Cl-]i in albino visual cortex neurons shifted to the pigmented rat brain value. In conclusion, our pharmacological experiments and subsequent single cell real time PCR analysis of the co-transporter mRNA demonstrated that the inhibitory deficit present in the albino visual cortical network is almost exclusively mediated by NKCC1.ConclusionOur findings suggest that blocking of NKCC1 in albino visual cortex neurons could improve processing in visual cortex and therefore might be beneficial for vision in albinos.
Highlights
During development the switch from a depolarizing to a hyperpolarizing action of GABA is a consequence of a decrease of the Na+-K+-2Cl- co-transporter (NKCC1, Cl--uptake) and increase of the K+-Cl- co-transporter (KCC2, Cl--extrusion) expression
To test whether changed GABAAR mediated currents observed in albino visual cortex neurons [22] is regulated by the two major cation-chloride co-transporters: KCC2 and NKCC1, the mRNAs for these transporters were studied in the albino and pigmented visual cortex neurons of postnatal day (P) 20–40 rats by single cell real time PCR
22 neurons were from albino and 5 from pigmented rat visual cortex. (p < 0,001, Chi-square test, data summarized in table 1)
Summary
During development the switch from a depolarizing to a hyperpolarizing action of GABA is a consequence of a decrease of the Na+-K+-2Cl- co-transporter (NKCC1, Cl--uptake) and increase of the K+-Cl- co-transporter (KCC2, Cl--extrusion) expression. While GABA is the main inhibitory transmitter in the adult brain, GABAergic transmission is excitatory during early postnatal development. This different action of GABA results from a reversed chloride concentration gradient with higher intracellular chloride concentration in immature neurons [7,8,9,10]. The developmental switch to an inhibitory action of GABA is a consequence of a decrease of NKCC1 and increase of (page number not for citation purposes)
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