Abstract
Mechanisms underlying Ca(2+) signaling during human myoblast terminal differentiation were studied using cell cultures. We found that T-type Ca(2+) channels (T-channels) are expressed in myoblasts just before fusion. Their inhibition by amiloride or Ni(2+) suppresses fusion and prevents an intracellular Ca(2+) concentration increase normally observed at the onset of fusion. The use of antisense oligonucleotides indicates that the functional T-channels are formed by alpha1H subunits. At hyperpolarized potentials, these channels allow a window current sufficient to increase [Ca(2+)](i). As hyperpolarization is a prerequisite to myoblast fusion, we conclude that the Ca(2+) signal required for fusion is produced when the resting potential enters the T-channel window. A similar mechanism could operate in other cell types of which differentiation implicates membrane hyperpolarization.