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- Alomone Labs TRAM 34 blocks KCa3.1 currents in stably transfected 293T cells.Currents were elicited by 150 ms voltage ramp from -120 mV to +60 mV, applied every 10 sec using whole-cell voltage clamp technique (Vh -80 mV). A. Superimposed traces of KCa3.1 currents (plotted against the ramp voltage) measured under control conditions and following 2 minutes perfusion of 50 nM, 250 nM, and 1 μM TRAM 34 (#T-105) as indicated. B. Time course of KCa3.1 current (at 0 mV) amplitude change as a result of the application of raising concentrations of TRAM 34 (perfusion duration indicated by the horizontal bar, concentration as indicated).
- 1. Gutman, G. A. et al. Calcium-Activated Potassium Channels. Last modified on 2011-01-31. Accessed on 2011-06-22. IUPHAR database (IUPHAR-DB).
- 2. Wulff, H. et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 8151.
- 3. Beeton, C. et al. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 13942.
- 4. Grgic, I. et al. (2005) Arterioscler. Thromb. Vasc. Biol. 25, 704.
- 5. Tharp, D.L. et al. (2008) Arterioscler. Thromb. Vasc. Biol. 28, 1084.
- 6. Jager, H. et al. (2004) Mol. Pharmacol. 65, 630.
KCa3.1 (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 KV channels, that is six transmembrane domains and intracellular N- and C-termini. KCa3.1 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 KCa3.1 channel inhibitor; 50 nM blocks KCa3.1 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 KCa3.1 channels in different physiological systems, ranging from activation of T lymphocytes to migration of endothelial cells3-4.
By using TRAM 34 it was demonstrated that proliferation of vascular endothelial cells and angiogenesis in vivo are mediated via KCa3.1 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 KCa3.1 expression in the former as well as in samples from pancreatic cancer patients6.
TRAM 34 (#T-105) is a highly pure, synthetic, and biologically active compound.