α1 subunit also determines the type of calcium channel. The β, α2δ, and γ subunits, present in only some types of calcium channels, are auxiliary subunits that play secondary roles in the channel. α1 Subunit The α1 subunit of T-type calcium channels is similar in structure to the α subunits of K+(potassium ion) channels, Na+(sodium ion) channels, and other Ca2+(calcium ion) channels. The α1 subunit is composed of four domains (I-IV), with each domain containing 6 transmembrane segments (S1-S6). The hydrophobic loops between the S5 and S6 segments of each domain form the pore of the channel. The S4 segment contains a high quantity of positively charged residues and functions as the voltage sensor of the channel opening or closing based on the membrane potential. The exact method by which the S4 segment controls the opening and closing of the channel is currently unknown. Auxiliary subunits The β, α2δ, and γ subunits are auxiliary subunits that affect channel properties in some calcium channels. The α2δ subunit is a dimer with an extracellular α2 portion linked to a transmembrane δ portion. The β subunit is an intracellular membrane protein. The α2δ and β subunits have an effect on the conductance and kinetics of the channel. The γ subunit is a membrane protein that has an effect on the voltage sensitivity of the channel. Current evidence shows that isolated T-type α1 subunits have similar behavior to natural T-type channels, suggesting that the β, α2δ, and γ subunits are absent from T-type calcium channels and the channels are made up of only an α1 subunit. Variation There are three known types of T-type calcium channels, each associated with a specific α1 subunit. Pathology When these channels are not functioning correctly, or are absent from their usual domains, several issues can result. Cancer T-type Calcium channels are expressed in different human cancers such as breast, colon, prostate, insulinoma, retinoblastoma, leukemia, ovarian, and melanoma, and they also play key roles in proliferation, survival, and the regulation of cell cycle progression in these forms of cancer . This was demonstrated through studies that showed that down regulating T-type channel isoforms, or just blocking the T-type calcium channels caused cytostatic effects in cancer cells such as gliomas, breast, melanomas, and ovarian, esophageal, and colorectal cancers . Some of the most notorious forms of cancer tumors contain cancer stem cells (CSC), which makes them particularly resistant to any