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  • The effects of tetrahexyl ammonium cations (THA+) on inositol 1,4,5-trisphosphate-induced calcium release from porcine cerebellar microsomes: THA+ can induce calcium release selectively from the InsP3-sensitive calcium stores.

The effects of tetrahexyl ammonium cations (THA+) on inositol 1,4,5-trisphosphate-induced calcium release from porcine cerebellar microsomes: THA+ can induce calcium release selectively from the InsP3-sensitive calcium stores.

Biochimica et biophysica acta (1993-10-10)
L G Sayers, F Michelangeli
ABSTRACT

In this study we show that the potassium-channel blocker tetrahexyl ammonium chloride (THA+) is able to inhibit inositol 1,4,5-trisphosphate (InsP3)-induced calcium release in an apparently biphasic fashion with a IC50 of 3 microM. This inhibition was not alleviated by valinomycin and, therefore, is not consistent with the blocking of K+ counter-ion movement, an observation initially made by Palade et al. (Palade, P., Dettbarn, C., Volpe, P., Alderson, B. and Otero, A.S (1989) Mol. Pharmacol. 36, 664-672). THA+ affected quantal calcium release by reducing the amount of calcium released by InsP3, but did not greatly affect the concentration of InsP3 required to cause half-maximal calcium release. THA+ did not affect the metabolism of InsP3 or its binding to porcine cerebellar microsomes. THA+ could also itself induce calcium release. At concentrations below 100 microM, THA+ appears to release Ca2+ selectively from the InsP3-sensitive calcium stores, since prior depletion of these stores with supramaximal doses of InsP3 abolishes this response. At higher THA+ concentrations (above 100 microM) Ca2+ is released non-selectively from all stores. THA+ has no effect on the Ca(2+)-ATPase activity at concentrations below 100 microM, indicating that selective THA(+)-induced Ca2+ release is not due to non-specific inhibition of the microsomal Ca2+ pumps and does not affect Ca2+ leakage. A number of pharmacological modulators of intracellular calcium channels were also tested on THA(+)-induced calcium release with little effect, except for spermidine which reduced this release by up to 50%. Our observations are consistent with the view that THA+, at concentrations below 100 microM, selectively releases calcium from the InsP3-sensitive calcium stores.

MATERIALS
Product Number
Brand
Product Description

Supelco
Tetrahexylammonium hydrogensulfate, suitable for ion pair chromatography, LiChropur, ≥99.0% (T)
Sigma-Aldrich
Tetrahexylammonium hydrogensulfate, ≥98.0% (T)
Sigma-Aldrich
Tetrahexylammonium bromide, 99%
Sigma-Aldrich
Tetrahexylammonium chloride, 96%
Supelco
Tetrahexylammonium bromide, suitable for ion pair chromatography, LiChropur, ≥99.0% (AT)
Sigma-Aldrich
Tetrahexylammonium hydroxide solution, ~40% in H2O (T)
Sigma-Aldrich
Tetrahexylammonium iodide, ≥99.0% (AT)
Sigma-Aldrich
Tetrahexylammonium hydroxide solution, ~10% in methanol (T)

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