Whole cell patch-clamp experiments were undertaken to define the basal K⁺conductance(s) in human erythroleukemia cells and its contribution to the setting of resting membrane potential. Experiments revealed a non-voltage-activated, noninactivating K⁺current. The magnitude of the current recorded under whole cell conditions was inhibited by an increase in free intracellular Mg²⁺concentration. Activation or inactivation of the Mg²⁺-inhibited K⁺current (MIP) was paralleled by activation or inactivation of a Mg²⁺-inhibited TRPM7-like current displaying characteristics indistinguishable from those reported for molecularly identified TRPM7 current. The MIP and TRPM7 currents were inhibited by 5-lipoxygenase inhibitors. However, inhibition of the MIP current was temporally distinct from inhibition of TRPM7 current, allowing for isolation of the MIP current. Isolation of the MIP conductance revealed a current reversing near the K⁺equilibrium potential, indicative of a highly K⁺-selective conductance. Consistent with this finding, coactivation of the nonselective cation current TRPM7 and the MIP current following dialysis with nominally Mg²⁺-free pipette solution resulted in hyperpolarized whole cell reversal potentials, consistent with an important role for the MIP current in the setting of a negative resting membrane potential. The MIP and TRPM7-like conductances were constitutively expressed under in vivo conditions of intracellular Mg²⁺, as judged by their initial detection and subsequent inactivation following dialysis with a pipette solution containing 5 mM free Mg²⁺. The MIP current was blocked in a voltage-dependent fashion by extracellular Cs⁺and, to a lesser degree, by Ba²⁺and was blocked by extracellular La³⁺and 2-aminoethoxydiphenyl borate. MIP currents were unaffected by blockers of ATP-sensitive K⁺channels, human ether-à-go-go-related gene current, and intermediate-conductance Ca²⁺-activated K⁺channels. In addition, the MIP current displayed characteristics distinct from conventional inwardly rectifying K⁺channels. A similar current was detected in the leukemic cell line CHRF-288-11, consistent with this current being more generally expressed in cells of leukemic origin.