rTertiapin

rTertiapin

A Peptide Blocker of Inward Rectifier (K_ir) K⁺ Channels

A continuous current trace recorded at -80 mV holding potential, from an oocyte  injected with Kir3.1/3.4 combination. Kir currents are downward deflections, activated by perfusion of High K+ containing solution (HK (in mM): 74 mM NaCl, 24 mM KCl,  1 mM MgCl2, 1.8 mM CaCl2 and 5 HEPES, pH=7.4), the point of application is indicated  at the top of the trace with a black arrow. While activated, increasing concentrations (in nM) of rTertiapin, were applied (bars at the bottom of the trace). Control recordings (prior to activation of Kir channels) were carried out with ND 96 solution.

Native Tertiapin was originally isolated from Apis mellifera bee venom.  Native and synthetic Tertiapin blocks a range of inward rectifier K⁺ channels. (K_ir), in particular ROMK1 (K_ir1.1, IC₅₀=2nM) and GIRK (K_ir3 family, IC₅₀ for the K_ir3.1/3.4 heteromer was 8.6 nM) but with no effect on K_ir2 family members.¹  In accordance, it was shown to inhibit acetylcholine induced K⁺ currents in heart.^2,3

rTertiapin is a recombinant peptide expressed in and extracted from E. coli and purified to homogeneity. rTertiapin is as active as rTertiapin-Q (#RTT-170), a derivative of Tertiapin in which the oxidation-liable methionine is replaced by a glutamine residue.⁶