KCa and Ca2+ channels: The complex thought

Abstract

Potassium channels belong to the largest and the most diverse super-families of ion channels. Among them, Ca(2+)-activated K(+) channels (KCa) comprise many members. Based on their single channel conductance they are divided into three subfamilies: big conductance (BKCa), intermediate conductance (IKCa) and small conductance (SKCa; SK1, SK2 and SK3). Ca(2+) channels are divided into two main families, voltage gated/voltage dependent Ca(2+) channels and non-voltage gated/voltage independent Ca(2+) channels. Based on their electrophysiological and pharmacological properties and on the tissue where there are expressed, voltage gated Ca(2+) channels (Cav) are divided into 5 families: T-type, L-type, N-type, P/Q-type and R-type Ca(2+). Non-voltage gated Ca(2+) channels comprise the TRP (TRPC, TRPV, TRPM, TRPA, TRPP, TRPML and TRPN) and Orai (Orai1 to Orai3) families and their partners STIM (STIM1 to STIM2). A depolarization is needed to activate voltage-gated Ca(2+) channels while non-voltage gated Ca(2+) channels are activated by Ca(2+) depletion of the endoplasmic reticulum stores (SOCs) or by receptors (ROCs). These two Ca(2+) channel families also control constitutive Ca(2+) entries. For reducing the energy consumption and for the fine regulation of Ca(2+), KCa and Ca(2+) channels appear associated as complexes in excitable and non-excitable cells. Interestingly, there is now evidence that KCa-Ca(2+) channel complexes are also found in cancer cells and contribute to cancer-associated functions such as cell proliferation, cell migration and the capacity to develop metastases. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau.

Potassium fluxes across the endoplasmic reticulum and their role in endoplasmic reticulum calcium homeostasis

“…Calcium-activated potassium channels are divided into big conductance Ca 2+ -sensitive K + (BK Ca ), intermediate conductance Ca 2+ -sensitive K + (IK Ca ) and small conductance calciumsensitive K + (SK Ca ) channels based on their K + conductance (for review see [47]). BK Ca channels are activated by membrane depolarization and/or elevated cytosolic Ca 2+ [48,49].…”

SK3/TRPC1/Orai1 complex regulates SOCE-dependent colon cancer cell migration: a novel opportunity to modulate anti-EGFR mAb action by the alkyl-lipid Ohmline

“…Store operated Ca 2+ entry (SOCE), is an ubiquitous Ca 2+ entry pathway that is mediated by the interaction of a Ca 2+ sensor at the endoplasmic reticulum (STIM1) and the plasma membrane channels Orai1. To reduce energy consumption and for a tighter regulation of their activities, Ca 2+ channels appear to be associated with Ca 2+ -activated K + channels to form complexes [11]. In tumor cells these complexes contribute to several cancer associated functions such as cell proliferation, cell migration and the capacity to develop metastases [11, 12].…”

“…To reduce energy consumption and for a tighter regulation of their activities, Ca 2+ channels appear to be associated with Ca 2+ -activated K + channels to form complexes [11]. In tumor cells these complexes contribute to several cancer associated functions such as cell proliferation, cell migration and the capacity to develop metastases [11, 12]. We have proposed that theses complexes are spatially segregated in nanodomains such as lipid-rafts [13].…”

Down-Regulation of Ca2+-Activated K+ Channel KCa1.1 in Human Breast Cancer MDA-MB-453 Cells Treated with Vitamin D Receptor Agonists

“…In cancer cells, the dysregulation of K Ca channels is associated with key aspects of proliferation, migration, and invasion during metastasis [19,20,21]. Based on single-channel conductance, K Ca channels have been classified into large-conductance K Ca 1.1, small-conductance K Ca 2.x (2.1–2.3), and intermediate-conductance K Ca 3.1 channels.…”