cancer therapy . Furthermore, there is evidence that suggests that the presence of the CSC in human tumors may be associated with the expression of T-type calcium channels in the tumors. Epilepsy The major disease that involves the T-type calcium channel is absence epilepsy. This disease is caused by mutations of T-type calcium channel itself. Individuals with absence seizures have brief periods of behavioral arrest and unresponsiveness. Experiments on the Genetic Absence Epilepsy Rat of Strasbourg (GAERS) suggested that absence epilepsy in the rat was linked to T-type channel protein expression. In fact, neurons isolated from the reticular nucleus of the thalamus of the GAERS showed 55% greater T-type currents, and these currents were attributed to an increase in the Cav3.2 mRNA, according to Tally et al. suggesting that T-type protein expression was up regulated in the GAERS. Further experiments on the GAERS showed that, indeed, the expression of T-type calcium channels play a key role in seizures caused by absence epilepsy in the GAERS. Also, other evidence suggest that T-type calcium channel expression is not only up regulated in absence epilepsy, but also in other forms of epilepsy as well. The first-line treatments for childhood absence epilepsy, valproate and ethosuximide, are both blockers of T-type calcium channels; the second-line treatment, lamotrigine, although not a T-type calcium channel blocker, does inhibit high-voltage activated calcium channels. Pain The Cav3.2 isoform of T-type calcium channels has been found to involve in pain in animal models with acute pain and chronic pain: neuropathic pain (PDN), inflammatory pain and visceral pain. Parkinson's disease Increased neuronal bursting occurs throughout the central motor system in both human forms and animals models of Parkinson's disease. T-type calcium channels are highly expressed in basal ganglia structures as well as neurons in the motor areas of the thalamus and are thought to contribute to normal and pathological bursting by means of low-threshold spiking. Basal ganglia recipient neurons in the thalamus are particularly interesting because they are directly inhibited by the basal ganglia output. Consistent with the standard rate model of the basal ganglia, the increased firing in basal ganglia output structures observed in Parkinson's disease would exaggerate the inhibitory tone in thalamocortical neurons. This may provide the necessary hyperpolarization to de-inactivate T-type calcium channels, which can result in rebound spiking. In normal behavior, bursting likely plays a role in increasing the likelihood of synaptic transmission, initiating state changes between