Possible transport mechanisms accounting for the cellular accumulation of Cl⁻ in pH 7.0 (A) or pH 4.0 (B) media containing 10 μM Cl⁻. The elevated cellular Cl⁻ content is proposed to be a consequence of two processes. (1)Influx across the plasma membrane via a high affinity Cl⁻ transporter (HACT), which is regulated by a mechanism that includes Yhl008c (depicted here on the plasma membrane, but the actual cellular location is not known). The Cl⁻ gradient across the plasma membrane is higher at extracellular pH 4.0 than at pH 7, consistent with H⁺–Cl⁻ cotransport across the plasma membrane. The dashed arrow represents downhill efflux of Cl⁻ through a pathway that is unknown but must be very slow in a low Cl⁻ medium (Fig. 5 B). (2) Sequestration of Cl⁻ in the vacuole or prevacuolar compartment by a process that is powered by the V-ATPase (Vma), with Cl⁻ transport (probably as Cl⁻/H⁺ exchange; see text) through Gef1p, and the pH gradient modulated by Nhx1p.