Fig. 1.

An increase in intracellular Cl^– switches the GABA_A-mediated hyperpolarization to depolarization in the pre-sympathetic PVN neurons of SHRs. The homeostasis of intracellular Cl^– is balanced by the counterpart Cl^– co-transporters NKCC1 and KCC2. NKCC1 imports Cl^– to increase [Cl^–]_i, whereas KCC2 exports Cl^– to decrease [Cl^–]_i. In SHRs, an increase in NKCC1 activity elevates the [Cl^–]_i, which shifts the GABA reversal potential above the resting membrane potential. Thus, activation of GABA_A leads to Cl^– outflow to induce GABA_A-mediated depolarization rather than hyperpolarization under physiological conditions.