Cell cycle-dependent expression of Kv1.5 is involved in myoblast proliferation

Abstract

Voltage-dependent K+ channels (Kv) are involved in the proliferation of many types of cells, but the mechanisms by which their activity is related to cell growth remain unclear. Kv antagonists inhibit the proliferation of mammalian cells, which is of physiological relevance in skeletal muscle. Although myofibres are terminally differentiated, some resident myoblasts may re-enter the cell cycle and proliferate. Here we report that the expression of Kv1.5 is cell-cycle dependent during myoblast proliferation. In addition to Kv1.5 other Kv, such as Kv1.3, are also up-regulated. However, pharmacological evidence mainly implicates Kv1.5 in myoblast growth. Thus, the presence of S0100176, a Kv antagonist, but not margatoxin and dendrotoxin, led to cell cycle arrest during the G1-phase. The use of selective cell cycle blockers showed that Kv1.5 was transiently accumulated during the early G1-phase. Furthermore, while myoblasts treated with S0100176 expressed low levels of cyclin A and D1, the expression of p21cip-1 and p27kip1, two cyclin-dependent kinase inhibitors, increased. Our results indicate that the cell cycle-dependent expression of Kv1.5 is involved in skeletal muscle cell proliferation. © 2008 Elsevier B.V. All rights reserved.