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 G(1)-phase. The use of selective cell cycle blockers showed that Kv1.5 was transiently accumulated during the early G(1)-phase. Furthermore, while myoblasts treated with S0100176 expressed low levels of cyclin A and D(1), the expression of p21(cip-1) and p27(kip1), 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.

Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness

“…In addition, Kv1.5 expression also increased in LMS. Both results are in agreement with previous reports demonstrating that Kv1.5 and Kv1.3 play a role in skeletal and smooth muscle cell proliferation (2,3,11).…”

“…Kv channels, which control cell excitability in muscle, also contribute to myoblast proliferation (2,11). In this study, we have shown for the first time that the expression of Kv1.3 and Kv1.5 increased in smooth muscle tumorigenesis in a close correlation with malignancy.…”

“…Kv1.5 is involved in skeletal muscle cell proliferation (11). Unlike Kv1.5, Kv1.3 governs macrophage cell growth (14), but plays no substantial role in skeletal myoblast proliferation (11). In a recent study, we observed a correlation of Kv1.3 and Kv1.5 expression with tumor malignancy in rhabdomyosarcomas (16).…”

“…The voltage-dependent Kv1.3 and Kv1.5 channels are involved in cell proliferation, and expression remodeling has been described during neoplastic growth (5,9). A number of tissues, such as brain, muscle and the immune system, co-express the two channels (10)(11)(12). Kv1.3 abundance is generally downregulated, whereas Kv1.5 expression is enhanced in several types of human cancer (5,9,13).…”

“…Kv1.3 and Kv1.5 increase during myoblast proliferation (11). Kv1.5 is the main subunit in skeletal myoblasts, whereas Kv1.3 is critical in smooth muscle (2,3).…”