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

Summary

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 nm 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 nm 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.