Effects of Ca2+ are most drastic at G1 phase of the cell cycle, where there is an increased expression of calmodulin and Ca2+-calmodulin-sensitive Cyclin D/CDK4 (Kahl and Means, 2003). However, cytoplasmic Ca2+ concentrations must be regulated such that it is high only when it needs to be, because a vital part of calmodulin-dependent kinase function is in its regulated stimulation. Persistent stimulation can cause modifications in calmodulin sensitiyity, such that a persistent high intracellular Ca2+ will eventually make calmodulin less sensitive to calcium ions (Kahl and Means, 2003). In addition, if neuronal CaM-kinases II are constantly activated, catecholamines cannot serve as neurotransmitters because there is no catecholamine concentration potential that indicates transmitted signal. If glycogen synthesis is constantly inhibited, chemical energy cannot be stored by the body in the form of glycogen (Alberts, et al., 2007 ).One of the major ways through which cytoplasmic Ca2+ concentrations are regulated is through T-type calcium channels.
T-type calcium channels are a group of low-voltage activated calcium channels. It has the characteristic six transmembrane alpha helices around a central pore. They open in response to even small membrane depolarization. Just like the enzymes it regulates, T-type calcium channels are also regulated. They are activated by cAMP-dependent protein kinase (PKA), which is directed to the phosphorylation site by an adapter called A-kinase anchor protein (AKAP). It is also regulated by intracellular Ca2+ concentration through calmodulin. Aside from those, protein kinase C can also activate T-type calcium channels. However, the activity of protein kinase C is counteracted by G-protein coupled receptors (Felix, 2005).
Because of the role of intracellular Ca2+ concentration to cell cycle, T-type calcium channels are associated with cell proliferation. Among normally differentiating cells which do not proliferate, expression of