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 was evaluated by examining resting membrane potential and timing of expression of K+ currents at three stages of differentiation of human myogenic cells: undifferentiated myoblasts, fusion-competent myoblasts (FCMBs), and freshly formed myotubes. 2. Two K+ currents contribute to a hyperpolarization of myoblasts prior to fusion: I-K(NI), a noninactivating delayed rectifier, and I-(KIR), an inward rectifier. 3. I-K(NI) density is low in undifferentiated myoblasts, increases in FCMBs and declines 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 Ba2+ 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 voltage determined by I-K(NI) (-32 mV). 6. Cs+ and Ba2+ ions reduce myoblast fusion. 7. It is hypothesized that the I-K(IR)-mediated hyperpolarization allows FCMBs to recruit Na+, K+ and T-type Ca2+ channels which are present in these cells and would otherwise be inactivated. FCMBs, rendered thereby capable of firing action potentials, could amplify depolarizing signals and may accelerate fusion.