The secret life of ion channels: Kv1.3 potassium channels and proliferation

Abstract

Kv1.3 channels are involved in the switch to proliferation of normally quiescent cells, being implicated in the control of cell cycle in many different cell types and in many different ways. They modulate membrane potential controlling K fluxes, sense changes in potential, and interact with many signaling molecules through their intracellular domains. From a mechanistic point of view, we can describe the role of Kv1.3 channels in proliferation with at least three different models. In the "membrane potential model," membrane hyperpolarization resulting from Kv1.3 activation provides the driving force for Ca influx required to activate Ca-dependent transcription. This model explains most of the data obtained from several cells from the immune system. In the "voltage sensor model," Kv1.3 channels serve mainly as sensors that transduce electrical signals into biochemical cascades, independently of their effect on membrane potential. Kv1.3-dependent proliferation of vascular smooth muscle cells (VSMCs) could fit this model. Finally, in the "channelosome balance model," the master switch determining proliferation may be related to the control of the Kv1.3 to Kv1.5 ratio, as described in glial cells and also in VSMCs. Since the three mechanisms cannot function independently, these models are obviously not exclusive. Nevertheless, they could be exploited differentially in different cells and tissues. This large functional flexibility of Kv1.3 channels surely gives a new perspective on their functions beyond their elementary role as ion channels, although a conclusive picture of the mechanisms involved in Kv1.3 signaling to proliferation is yet to be reached.

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

“…Changes in ion channel and pump activities are the major determinants of cell membrane electrical changes in plants (Pickard & Ding, ; Véry & Sentenac, ; Shomer et al , ; Kinraide, ; Mishra et al , ; Lim et al , ; Catterall et al , ; Flucher & Tuluc, ; Perez Garcia et al , ). Indeed, calcium channel inhibitors, such as methoxyverapamil or GdCl 3 , efficiently reduced or blocked depolarization after cell ablation, as did inhibitors of chloride and potassium channels and proton pumps (Fig A and B).…”

Myocardin-Dependent Kv1.5 Channel Expression Prevents Phenotypic Modulation of Human Vessels in Organ Culture

“…Kv1.3 channel have been shown to be involved in cell proliferation in many cell types, including immune system cells, glial cells, VSMCs and cancer cells 36 . With the exception of T-lymphocytes, all these cells express other Kv1 channels, whose levels are also altered upon activation.…”

Ion Channels and Their Regulation in Vascular Smooth Muscle

“…By setting and controlling the membrane potential, these channels influence the levels of [Ca 2+ ] i and therefore, vascular smooth muscle contraction. Intriguingly, a subset of K + channels has also been linked to regulation of vascular smooth muscle proliferation (see recent review on this topic in [27,28]). Vascular smooth muscle cells express a wide variety of isoforms from several classes of K + channels, including K V , BK Ca , and K ir channels (see Figure 2).…”