Guinea pig Anti-TRPC6 Antibody

Transient receptor potential (TRP) channels are relatively non-selective ion channels enabling the exchange of cations down their electrochemical gradient. This exchange enables the intracellular rise in Na⁺ and Ca²⁺ concentration and ultimately in the cell membrane depolarization, important for action potential propagation and muscle contraction¹. They are activated by an extremely broad range of stimuli namely, temperature, voltage, pH, endocrine factors as well as signaling molecules².

The TRP channel family is composed of 28 members divided in 7 subgroups: TRPV, TRPC, TRPM, TRPA, TRPN, TRPP and TRPML. All members of the TRP family form tetramers and could heterhomultimerize. They have 6 transmembrane (TM) domains, and a pore domain between the fifth (S5) and sixth (S6) transmembrane domains. In general, TRP channels enable the passage of either Na⁺ or Ca²⁺ ions with little or no preference. However, some channels do exhibit some selectivity. Also, TRP channels do not display the positive charges in the transmembrane domain number 4 voltage-sensing domain like most voltage sensitive channels, although they do display voltage dependency³. In addition, TRP channels have in the C-terminal intracellular region to the S6 domain a TRP domain comprising 25 amino acids that is more or less conserved among most TRP channels. Within the TRP domain, there is a TRP box composed of six amino acids, and TRP box 2 – a proline rich domain^1,3. The TRP domain seems to be responsible for the binding of PIP₂, a phospholipid important for the regulation of channel activity⁴.

The TRPC subfamily is further divided into the following: TRPC1/4/5, TRPC3/6/7 and TRPC2¹. Activation of phospholipase C (PLC) ultimately leads to the formation of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) via hydrolysis of PIP₂. The increase in concentration of these intracellular second messengers leads to the activation of non-selective Ca²⁺ channels and an IP3-induced release of Ca²⁺ from intracellular stores⁵. The intracellular Ca²⁺ store depletion in turn activates Ca²⁺ specific channels to allow replenish intracellular Ca²⁺ levels. TRPCs are thought to be activated upon intracellular store Ca²⁺ depletion, and may function in concert with the recently identified Orai channel⁵. The TRPC3/6/7 class produces similar currents upon activation.

TRPC6 can form heterotetramers with TRPC3 and TRPC7. It is primarily expressed in brain, lung and muscle. High levels of expression of the channel were also found in human platelets. Recently it was reported that TRPC6 is also expressed in the kidney where a mutated channel has been implicated in kidney failure disease^6,7.