TRAM-34 is a highly selective inhibitor of KCa3.1 channel with IC50 value of 20 nM .
The Ca (2+)-binding protein calmodulin (CaM) confers Ca (2+) sensitivity to KCa3.1 of KCa3.1. On the basis of crystal structure obtained for the C-terminal region of the rat KCa2.2 channel (rSK2) with CaM that the binding of Ca (2+) to the CaM N-lobe results in CaM interlocking the C-terminal regions of two adjacent KCa3.1 subunits, leading to the formation of a dimeric structure. It is reported that many factors can increase KCa3.1, like balloon injury .
TRAM-34 is a KCa3.1 channel inhibitor and plays an important role in many diseases. When tested with human T cells, TRAM-34 treatment inhibited cells mobility and migration via blocking KCa3.1 channel . In coronary smooth muscle cells isolated by laser capture microdissection, delivery of TRAM-34 via balloon catheter significantly blocked the KCa3.1 increase . When tested with COS-7 cells, TRAM-34 inhibited KCa3.1 channel with Kd of 20 ± 3 nM and a Hill coefficient of 1.2 with 1 μM calcium in the pipette .
In male Wistar rat model of ischemic stroke, administration of TRAM-34 intraperitoneal (10 or 40 mg/kg, twice daily) for 7 days reduced infarction, neuronal death, microglia activation and neurological deficit via blocking KCa3.1 channel .
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