KCa and Ca2 + channels: The complex thought

•Features of calcium-activated potassium and calcium channels are described.•These channels form complexes in excitable and non-excitable cells.•These complexes reduce energy consumption for the fine regulation of calcium.•There is now evidence that these complexes are formed in cancer cells.•These complexes are associated to cancer cell migration and metastasis development.

Potassium channels belong to the largest and the most diverse super-families of ion channels. Among them, Ca2 +-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). Ca2 + channels are divided into two main families, voltage gated/voltage dependent Ca2 + channels and non-voltage gated/voltage independent Ca2 + channels. Based on their electrophysiological and pharmacological properties and on the tissue where there are expressed, voltage gated Ca2 + channels (Cav) are divided into 5 families: T-type, L-type, N-type, P/Q-type and R-type Ca2 +. Non-voltage gated Ca2 + 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 Ca2 + channels while non-voltage gated Ca2 + channels are activated by Ca2 + depletion of the endoplasmic reticulum stores (SOCs) or by receptors (ROCs). These two Ca2 + channel families also control constitutive Ca2 + entries. For reducing the energy consumption and for the fine regulation of Ca2 +, KCa and Ca2 + channels appear associated as complexes in excitable and non-excitable cells. Interestingly, there is now evidence that KCa–Ca2 + 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.