Suppression of the delayed rectifier type of voltage gated K+ outward current in megakaryocytes from patients with myelogenous leukemias.
In normal human megakaryocytes, we identified a delayed rectifier type of voltage-gated outward K+ current (DRK). In two human megakaryoblastic tumor cell lines (DAMI, CHRF-288-11) and the human erythroleukemia cell line (HEL) the DRK current was not detected. To determine if the absence of the DRK current in the tumor cells is the result of the underlying malignant state, we examined megakaryocytes from myelogenous leukemia patients. In 24 of 29 megakaryocytes from the myelogenous leukemia patients, the DRK current was greatly suppressed, whereas in the remaining 5 megakaryocytes a normal large amplitude DRK current was present. We had the opportunity to reexamine megakaryocytes from a patient with acute promyelocytic leukemia (M3), after chemotherapy. Whereas the DRK current was suppressed before treatment, the current reappeared after chemotherapy. Exposure to the adenylate cyclase activator, forskolin, caused the appearance of a voltage-gated outward current in the megakaryocytes of patients with acute myelogenous leukemia. This finding suggests either that the channels underlying the DRK current are present but somehow suppressed in megakaryocytes from these patients or that forskolin induces a different voltage-gated outward current. We suggest that the megakaryocytes from the myelogenous leukemia patients with suppressed DRK current are abnormal, whereas the others may be normal megakaryocytes. The suppression of the DRK current may be a contributory factor to the dysregulation of thrombopoiesis (Zittoun et al: Semin Hop Paris 44:183, 1968 and Rabellino et al: Blood 63:615, 1984) in myelogenous leukemias.
Kapural
L
L
Department of Physiology, University of Connecticut Health Center, Farmington 06030, USA.
Feinstein
M B
MB
O'Rourke
F
F
Fein
A
A
D000818:Animals; D001854:Bone Marrow Cells; D005576:Colforsin / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007951:Leukemia, Myeloid / Q000097:blood*; D008533:Megakaryocytes / Q000502:physiology*; D008564:Membrane Potentials; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015221:Potassium Channels; D005576:Colforsin; D011188:Potassium