TRAM 34

K_Ca3.1 (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. K_Ca3.1 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 channel¹.

TRAM 34 is a potent and selective K_Ca3.1 channel inhibitor; 50 nM blocks K_Ca3.1 channel expressed in COS-7 cells by over 50%². As such, it is a powerful pharmacological tool that enables the determination of the roles played by K_Ca3.1 channels in different physiological systems, ranging from activation of T lymphocytes to migration of endothelial cells^3-4.

By using TRAM 34 it was demonstrated that proliferation of vascular endothelial cells and angiogenesis in vivo are mediated via K_Ca3.1 channels⁴.

in vivo delivery of TRAM 34 via balloon catheter prevented porcine coronary smooth muscle phenotypic modulation and limited subsequent vasculoproliferative diseases⁵.

10 mM 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_Ca3.1 expression in the former as well as in samples from pancreatic cancer patients⁶.