Question

In many neurons the equilibrium potential (E_Cl-) for Cl- is -70 mV, the extracellular concentration of Cl- [Cl-]_o is about 110 mM and the intracellular concentration of Cl- [Cl-]_i is about 7-9 mM. Given that the intracellular concentration of Cl- decreases to 4-5 mM, discuss how this may influence the effect of GABA on GABA_A-receptors expressing neurons. How may GABA agonists through the GABA_A receptors affect the CNS if the [Cl-]_i is decreased?

I have calculated the equilibrium potential using Nernst equation if the Cl- decreases to go from -70 mV to about -85 mV.

Answer 1

During development GABA action shifts from depolarizing to hyperpolarizing.The polarity depends upon the intracellular chloride concentration.Which is controlled by the action of Na+,K+,2Cl- and cotransporters.

Depolarizing GABA action can lead to inhibition due to the presence of shunting inhibition that critically depends on the chloride driving force and the synapse location,in brain chloride extrusion operated by KCC2 and the the concentration of Cl- ion become low with consequent inhibitory action of GABA current.Such developmental chloride gradient inversion is assumed to occur in all neurons of the central nervous system.  

Equlibrium potential from -70 to -85=61.5xlog -70/-85= -1.3345