Abstract
There are seven mammalian thermo-sensitive transient receptor potential channels (thermoTRPs). TRPM2 is a non-selective Ca2+-permeable cation channel in the TRP family of ion channels. Among the thermoTRPs, TRPM2 has been known to be activated by elevated temperature with a threshold of near 35°C, nicotinamide adenine dinucleotide (β-NAD+) and adenosine 5'-diphosphoribose (ADP-ribose). The current responses have been reported to be potentiated by combination of each ligand with heat. Furthermore, cyclic ADP-ribose (cADP-ribose) with heat also activates TRPM2 although cADP-ribose alone cannot activate the channel. To date, it is known that non-steroidal anti-inflammatory drug, flufenamic acid (FFA) and antifungal agents, econazole and clotrimazole inhibit TRPM2. However, the inhibition was gradual and irreversible. Here we show that 2-aminoethoxydiphenyl borate (2-APB) exhibits instantaneous blocking of TRPM2 channel activity with a reversible fashion using a patch-clamp technique in HEK293 cells expressing human TRPM2. 2-APB blocked TRPM2 responses evoked not only by its ligand but also by ligand with heat. Thus, 2-APB seems to be a more powerful and effective tool in studying the role of TRPM2. [Jpn J Physiol 55 Suppl:S136 (2005)]
