Lysosomal Ion Channel Antibody Explorer Kit

Lysosomes are intracellular acidic organelles containing over 60 different types of hydrolases. They are responsible for the degradation of intracellular components from autophagy and of extracellular particles from endocytosis. Lysosomes contain a large number of membrane proteins, some of them being ion channels which play an important role in regulating membrane potential and lysosomal ionic homeostasis.
Thus far the following native ionic conductances have been revealed in single channel recordings and in whole-lysosomal recordings from artificially enlarged lysosomes: K⁺, Na⁺, Cl^-, Ca²⁺ and H⁺.

Although voltage dependent K⁺ conductances have been recorded their nature remains unclear at the moment. There are several types of H⁺ conductances: a proton leak conductance, most probably, through a H⁺-dependent catabolite exporter and an electrogenic V-ATPase H⁺ pump. A depolarization-activated H⁺ conductance which is insensitive to Zn²⁺ and activates rapidly whose channel is yet to be discovered. CIC-7 is coexpressed with Otsm1 and might be responsible for the lysosome’s native Cl^- conductance but this remains to be demonstrated in CIC-7/Otsm1 knockout mouse models. Two types of Na⁺ conductances have been recorded- a voltage dependent conductance through the TPC1 channel and a voltage independent current through the TPC2 channel. TPCs are ion channels with a two by six transmembrane structure and are widely expressed in humans.
The principal Ca²⁺ release channel in the lysosome is the TRPML channel. This channel consists of six putative transmembrane spanning domains (S1-S6) with the N and C termini facing the cytosol. The channel’s pore-loop region is between S5 and S6 and is hypothesized to form the channel gate.