[2] The distinct structures of T-type calcium channels are what allow them to conduct in these manners, consisting of a primary α1 subunit.
T-type calcium channels function to control the pace-making activity of the SA Node within the heart and relay rapid action potentials within the thalamus.
[3] Pharmacological evidence of T-type calcium channels suggest that they play a role in several forms of cancer,[4] absence epilepsy,[5] pain,[6] and Parkinson's disease.
[1] This is important in the aforementioned depolarization events in the pace-making activity of the sinoatrial (SA) Node in the heart and in the neuron relays of the thalamus so that quick transmission of action potentials can occur.
Although all of these functions of the T-type voltage gated calcium channel are important, quite possibly the most important of its functions is its ability to generate potentials that allow for rhythmic bursts of action potentials in cardiac cells of the sinoatrial node of the heart and in the thalamus of the brain.
[1][3] 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.
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 .
[13] Increased neuronal bursting occurs throughout the central motor system in both human forms and animals models of Parkinson's disease.
[14] 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.
In normal behavior, bursting likely plays a role in increasing the likelihood of synaptic transmission, initiating state changes between rest and movement, and might signal neural plasticity due to the intracellular cascades brought on by the rapid influx of calcium.
[17] While these roles are not mutually exclusive, most attractive is the hypothesis that persistent bursting promotes a motor state resistant to change, potentially explaining the akinetic symptoms of Parkinson's disease.
[6] T-type calcium channels represent an alternative approach to Parkinson's disease treatment as their primary influence is not concerning the central dopaminergic system.
For example, they offer great potential in reducing side effects of dopamine replacement therapy, such as levodopa-induced dyskinesia.
The co-administration of T-type calcium channel blockers with standard Parkinson's disease medications is most popular in Japan, and several clinical studies have shown significant efficacy.
[7] However, most of these drugs are experimental and operate in a non-specific manner, potentially influencing sodium channel kinetics as well as dopamine synthesis.