Studies of Ca2+ ATPase (SERCA) Inhibition

Abstract

The Ca(2+) transport ATPase of intracellular membranes (SERCA) can be inhibited by a series of chemical compounds such as Thapsigargin (TG), 2,5-di(tert-butyl)hydroquinone (DBHQ) and 1,3-dibromo-2,4,6-tris (methyl-isothio-uronium) benzene (Br(2)-TITU). These compounds have specific binding sites in the ATPase protein, and different mechanisms of inhibition. On the other hand, SERCA gene silencing offers a convenient and specific method for suppression of SERCA activity in cells. The physiological and pharmacological implications of SERCA inhibition are discussed.

TRPA1 Channels Mediate Cold Temperature Sensing in Mammalian Vagal Sensory Neurons: Pharmacological and Genetic Evidence

“…We also tested the potential involvement of internal stores and calcium-induced calcium release on the cold-evoked [Ca 2ϩ ] i elevations. To this end, neurons were incubated for 60 min in 1 M thapsigargin, an inhibitor of sarco/endoplasmic reticulum Ca 2ϩ /ATPase pump that depletes calcium stores (Inesi et al, 2005). After thapsigargin treatment mean basal [Ca 2ϩ ] i was substantially elevated (264 Ϯ 19 nM compared with 96 Ϯ 2 nM; unpaired t test, p Ͻ 0.001) and mean [Ca 2ϩ ] i elevation during cooling was 304 Ϯ 60 nM (n ϭ 14), with the signal clearly outlasting the temperature drop (Fig.…”

Detection of Near-membrane Calcium Ions in Live Tissues with a Two-Photon Fluorescent Probe

“…The TPEF intensities were more enhanced and the decay rates were slower (Figure 8d), when PTH was added after treating the cells for 10 min with thapsigarin (5 µM), an inhibitor that blocks the re-entry of Ca 2+ into intracellular store formed by endoplasmic reticulum (ER). 13 These results indicate that ACaCL is clearly capable of detecting We then investigated the utility of this probe in tissue imaging. TPM images were obtained from a part of fresh rat hippocampal slice incubated with 10 mM ACaCL for 30 min at 37 o C. The bright field image reveals the CA1 and CA3 regions as well as the dentate gyrus (DG, Figure 4a).…”

SERCA Inhibition Limits the Functional Effects of Cyclic GMP in Both Control and Hypertrophic Cardiac Myocytes

“…Inhibitors of SERCA such as CPA and thapsigargin have been used to block Ca 2+ uptake by SERCA into the sarcoplasmic reticulum and to maintain intracellular cytosolic Ca 2+ levels [23] . These agents can dramatically affect calcium transients in cardiac myocytes.…”