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T-Type Calcium Channels

Description/Background

T-Type Calcium Channels are low-voltage activated calcium channels that are highly selective and open during membrane depolarization. T-Type channels are generally expressed in the dendrites^{[citation needed]}of neurons indicating that they play a key role in synaptic integration ^{[citation needed]}. T-Type channels are also mostly located in sensory neurons in both the efferent and afferent pathways, indicating that they also play an important role in neurons that infer pain, and relay it (2). From this, it is evident that T-Type Calcium Channels play important roles in many parts of the nervous system and sensory relay pathway.

Structure and Variation

T-type calcium channels are composed of 5 subunits: and alpha-1 subunit, alpha-2 subunit, a delta subunit, a gamma subunit, and a beta subunit. The alpha-1, gamma, and delta subunits are transmembrane structures; the alpha-2 subunit is extracellular, while the beta subunit is intracellular.

Function

Like any other channel in a cell membrane, the primary function of the T-Type Calcium channel is to allow passage of ions, in this case Calcium, through the membrane when the channel is activated. When membrane depolarization occurs in a cell membrane where these channels are embedded, they open and allow Calcium to enter the cell which leads to several different cellular events depending on where in the body the cell is found. As a member of the CaV3 subfamily of Voltage-gated Calcium channels, the function of the T-Type channel is important for the repetitive firing of action potentials in cells with rhythmic firing patterns such as cardiac muscle cells and neurons in the thalamus. T-Type Calcium channels are activated in the same range as voltage-gated Sodium channels, which is at about -55 mV. Because of this very negative value at which these channels are activated and open, there is a large driving force for Calcium going into the cell. This is important in the aforementioned depolarization events in the pace-making activity of the SA Node in the heart and in the neuron relays of the thalamus.

Pharmacology

T-type calcium channels are subject to extensive research due to the fact that they are believed to play a role in various diseases. These diseases range from diabetes to epilepsy and even some forms of cancer. It has been reported that the the CaV3.2 isoform of T-type calcium channels is involved in sensitizing nociceptors of the DRG, which may cause the development of Peripheral Diabetic Neuropathy (PDN).^{[citation needed]}