Glioblastomas are characterized by altered expression of several ion channels that have important consequences in cell functions associated with their aggressiveness, such as cell survival, proliferation, and migration. Data on the altered expression and function of the intermediate-conductance calcium-activated K (KCa3.1) channels in glioblastoma cells have only recently become available. This paper aims to (i) illustrate the main structural, biophysical, pharmacological, and modulatory properties of the KCa3.1 channel, (ii) provide a detailed account of data on the expression of this channel in glioblastoma cells, as compared to normal brain tissue, and (iii) critically discuss its major functional roles. Available data suggest that KCa3.1 channels (i) are highly expressed in glioblastoma cells but only scantly in the normal brain parenchima, (ii) play an important role in the control of glioblastoma cell migration. Altogether, these data suggest KCa3.1 channels as potential candidates for a targeted therapy against this tumor. 1. Introduction Glioblastomas are the most common and aggressive among primary brain tumors. In spite of the intensive basic and clinical studies, only minor successes have been witnessed over the last decades. One-third of patients keep surviving no longer than one year from diagnosis, and average life expectancy remains dismal (12–15 months), even when radical surgical resection, chemo- and radiotherapy can be applied. The major problem with glioblastomas is their highly migratory and invasive potential into the normal brain tissue that prevents complete surgical removal of tumor cells and the extreme resistance of these cells to standard treatments [1]. To worsen the outcome of the disease is the presence in the tumor mass of a recently identified subpopulation of highly tumorigenic stem-like glioblastoma cells possessing even more invasive power, chemo- and radio-resistance than nonstem tumor cells, that are also thought to be responsible for the commonly observed tumor relapses [2–4]. Glioblastomas are characterized by a large number and variety of genetic mutations that heavily disregulate the major signaling pathways controlling cell survival, proliferation, differentiation, and invasion [5]. Among the disregulated pathways found in glioblastoma cells there are those controlling the expression of ion channels, transmembrane proteins endowed with a permeation pore that allows the passage of ions. Usually ion channels are selectively permeable to one particular ion and can open and close their permeation pore in response
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