Potassium channels in cell cycle and cell proliferation

Abstract

Normal cell-cycle progression is a crucial task for every multicellular organism, as it determines body size and shape, tissue renewal and senescence, and is also crucial for reproduction. On the other hand, dysregulation of the cell-cycle progression leading to uncontrolled cell proliferation is the hallmark of cancer. Therefore, it is not surprising that it is a tightly regulated process, with multifaceted and very complex control mechanisms. It is now well established that one of those mechanisms relies on ion channels, and in many cases specifically on potassium channels. Here, we summarize the possible mechanisms underlying the importance of potassium channels in cell-cycle control and briefly review some of the identified channels that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell-cycle progression.

Keywords: cancer; cell cycle; cell division; potassium channels; proliferation.

Figure 1.

Complete block of DNA synthesis, measures as [³H]thymidine incorporation in cells with fixed hyperpolarized membrane potential. Reproduced from [7] with permission. Open circles, control; black circles, manipulation of membrane potential.

Figure 2.

Schematic of the behaviour of the membrane potential along the cell cycle. Different potassium channels show variations of expression or activity through the cell cycle, thus shifting the membrane potential towards hyperpolarized values, close to the equilibrium potential for potassium, at the border between G1 and S-phases.

Figure 3.

K⁺ channels influence cell-cycle progression through permeation-related and non-canonical mechanisms. The former include cell volume regulation, modulation of membrane potential and generation of driving for Ca²⁺, while the latter rely on protein–protein interactions. K⁺ channel expression or function can in turn be regulated by progression through the cell cycle.