TRAM 34

TRAM 34. A Selective and Potent Blocker of K\\_Ca\\3.1 (SK4) Channels.
K\\_Ca\\3.1 (SK4, intermediate conductance Ca²⁺ activated K\\^+\\) is part of the Ca²⁺ activated K\\^+\\ channel family that share the characteristic of being activated by intracellular Ca²⁺. The channel has an intermediate conductance, is voltage insensitive and is activated by Ca²⁺ in the submicromolar range. The channel has a similar topology to that of K\\_V\\ channels, that is six transmembrane domains and intracellular N- and C-termini.пїЅ
K\\_Ca\\3.1 is widely expressed in epithelial, endothelial cells and cells of hematopoietic origin. In erythrocytes (red blood cells) it has been identified as the molecular correlate of the so-called Gardos channel.
TRAM 34 is a potent and selective K\\_Ca\\3.1 channel inhibitor; 50 nM blocks K\\_Ca\\3.1 channel expressed in COS-7 cells by over 50%.
As such, it is a powerful pharmacological tool that enables the determination of the roles played by K\\_Ca\\3.1 channels in different physiological systems, ranging from activation of T lymphocytes to migration of endothelial cells.

By using TRAM 34 it was demonstrated that proliferation of vascular endothelial cells and angiogenesis in vivo are mediated via K\\_Ca\\3.1 channels.
in vivo delivery of TRAM 34 via balloon catheter prevented porcine coronary smooth muscle phenotypic modulation and limited subsequent vasculoproliferative diseases.
10 μM TRAM 34, completely stopped proliferation of the human pancreatic cancer cell lines, (BxPC-3 MiaPaCa-2) while proliferation of PANC-1 cells was hardly affected by TRAM 34, which was well correlated to the elevated levels of K\\_Ca\\3.1 expression in the former as well as in samples from pancreatic cancer patients.
Ion Channel Modulators; K\\^+\\ Channel Blockers

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