Two-pore channel

[1][3] Some key roles of TPCs include calcium dependent responses in muscle contraction(s), hormone secretion, fertilization, and differentiation.

[citation needed] Disorders linked to TPCs include membrane trafficking, Parkinson's disease, Ebola, and fatty liver.

Therefore, these TPC channels have to be expressed in alternative compartments or organelles of the cell, such as plant vacuoles to be studied using the electrophysiological methods – especially the patch clamp technique.

Using these techniques, scientists have been able to collect significant qualitative data in order to make conclusions about mammalian TPC functions.

At the mouth of the TPC pore, there are four amino acid residues with negative charges that can interact with ions that pass through.

Voltage sensors, selectivity filter, and the gate work together in a coordinated manner to open and close TPCs for regulation of ion conductance.

[1]The VSD2 domain contains a normal voltage sensing motif, arginine residues R1, R2 and R3 and alpha helix S10,[16] in respect to other voltage-gated ion channels structures, but this domain adopts a distinct conformation in the resting state of a voltage sensor.

[1] Activation of TPCs is induced by a decrease in transmembrane potential, or by an increase in calcium concentrations in the cytosol.

The mechanism for channel opening is likely contributed to a combination of calcium concentrations, voltage, and phosphoregulation integration, in order to govern the conduction of ions through TPCs.

This is done by direct communication between the TPCs and mammalian/mechanistic targets of rapamycin (mTORs), which are associated with detecting levels of oxygen, nutrients, and energy in the cells and thus help with regulation of metabolism.

[17] TPCs regulate sodium and calcium ion conductance, intravasicular pH, and trafficking excitability.

[3][18] TPC2s are NAADP-gated calcium release channels where these TPC currents can be blocked by NAADP antagonists.

TPC trafficking activity has been noted to be conserved; but modifying TPCs affects transportation in the endocytotic pathway.

The influx of calcium is what regulates the fusion between the endosome and lysosomes and what mediates trafficking events.

As TPC2 plays a vital role in this specific mechanism of Parkinson's disease development, it may potentially be a therapeutic target.

[4] The Ebolavirus takes advantage of host cell endocytotic membrane trafficking, leaving TPCs as a potential drug target.

This is because tetradine blocks TPC functioning of calcium release and thus, the Ebolaviruses is contained within the endosomal network destined to be degraded by the lysosome.

The TPC mechanism once again allows the efflux of calcium for the fusion of the endosomes and lysosomes (where LDL is degraded).