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 S4 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 along with the recently identified Orai channel⁵. The TRPC3/6/7 class produces similar currents upon activation.

TRPC7 is activated by a broad range of hormones and neurotrophins, many of which activate PLC dependent pathways, via G-protein coupled receptors (GPCRs) or receptor tyrosine kinases (RTKs). Its expression is has been detected in dorsal root ganglia (DRGs), heart, uterine myometrium, keratinocytes and leukemic cells⁵.

In myocardial cells, TRPC7 has recently been shown to promote apoptosis, thereby becoming a contributing factor in the development of heart disease. Indeed, there is a strong correlation between the high expression level of TRPC7 and apoptosis in hearts from Dahl salt-sensitive rats which have suffered from heart failure^5,6.