Alterations in a voltage-gated K⁺ current during the differentiation of ML-1 human myeloblastic leukemia cells

A voltage-gated K⁺ current has been identified in ML1 human myeloid leukemia cells, with the use of the whole-cell patch-clamp technique. ML-1 cells proliferate in tissue culture as immature myeloblasts and can be induced to differentiate to nonproliferative monocyte/macrophages. In the myeloblastic cells, activation of the K⁺ current occurs upon depolarization of the membrane potential to above -40 mV; inactivation of this current is also voltage dependent and follows a simple exponential time course with a time constant (T_i) of 900 msec at 0 mV. The current is inhibited by 4-aminopyridine (IC₅₀ of 80 μm at 0 mV), but is much less sensitive to tetraethylammonium of Ba²⁺. In cells exposed to the differentiation-inducer 12-O-tetradecanoylphorbol-13-acetate (TPA), dramatic alterations in the K⁺ current occur: upon exposure to 10 n m TPA during whole-cell recording, the amplitude of the voltage-activated current initially increases (within 4 min) and later decreases (at approximately 30-50 min). Upon addition of 0.5 n m TPA to cells in tissue culture, the current shows suppressed activation and accelerated inactivation in the early stages of differentiation (10-fold decrease in T_i at approximately 7 hr) and is completely suppressed in the later stages (3 days). Thus, this voltage-gated K⁺ current is suppressed early in the induction of differentiation and associated loss of proliferation in myeloid ML-1 cells exposed to TPA; this parallels the fact that channels of a. similar type are activated upon the stimulation of proliferation in lymphoid cells exposed to mitogens. Taken together, these findings suggest a role for voltagegated K⁺ channels in cell proliferation, and for their suppression in the loss of proliferation that accompanies differentiation.