Voltage gating is intrinsic to Cx46 hemichannels. Shown are multichannel cell-attached patch recordings from a Cx46-expressing oocyte with (A) 1 mM Mg2+ present in the patch pipette and (B) with no added Mg2+ in the patch pipette. In both cases, Ca2+ was buffered to very low levels with EGTA. When the extracellular solution (patch pipette solution) contained 1 mM Mg2+, membrane hyperpolarization to −70 mV and depolarization to +90 mV produced reductions in current characteristic of loop gating and Vj gating, respectively. Currents were leak subtracted (dotted lines designate the 0 current level). When the extracellular solution was essentially devoid of external divalent cations, Vj gating at +90 mV was unaffected and loop gating at −70 mV was abolished, but application of a very large hyperpolarizing step to −160 mV caused a robust and rapid decrease in current. Although the current clearly declined toward zero, it remained very flickery and noisy. All currents were filtered at 1 kHz and data were acquired at 5 kHz.