ROLE OF AN INWARD RECTIFIER K+ CURRENT AND OF HYPERPOLARIZATION IN HUMAN MYOBLAST FUSION

1. The role of K+ channels and membrane potential in myoblast fusion w as evaluated by examining resting membrane potential and timing of exp ression of K+ currents at three stages of differentiation of human myo genic cells: undifferentiated myoblasts, fusion-competent myoblasts (F CMBs), and freshly formed myotubes. 2. Two K+ currents contribute to a hyperpolarization of myoblasts prior to fusion: I-K(NI), a noninactiv ating delayed rectifier, and I-(KIR), an inward rectifier. 3. I-K(NI) density is low in undifferentiated myoblasts, increases in FCMBs and d eclines in myotubes. On the other hand, I-K(IR) is expressed in 28% of the FCMBs and in all myotubes. 4. I-K(NI) is reversibly blocked by Ba 2+ or Cs+ 5. Cells expressing I-K(IR) have re ting membrane potentials of -65 mV. A block by Ba2+ or Cs+ induces a depolarization to a volta ge determined by I-K(NI) (-32 mV). 6. Cs+ and Ba2+ ions reduce myoblas t fusion. 7. It is hypothesized that the I-K(IR)-mediated hyperpolariz ation allows FCMBs to recruit Na+, K+ and T-type Ca2+ channels which a re present in these cells and would otherwise be inactivated. FCMBs, r endered thereby capable of firing action potentials, could amplify dep olarizing signals and may accelerate fusion.