Histamine-evoked Ca2+ oscillations in HeLa cells are sensitive to methylxanthines but insensitive to ryanodine

Abstract

The relative contribution of inositol-trisphosphate(InsP3)-sensitive and InsP3-insensitive Ca2+ stores to the agonist-evoked oscillatory release of Ca2+ in HeLa cells was investigated using fura-2 cytosolic Ca2+ measurements and whole-cell recordings of Ca(2+)-activated K+ currents [K(Ca2+)]. The experimental approach chosen consisted in studying the effects on Ca2+ oscillations of a variety of pharmacological agents such as ryanodine, ruthenium red, caffeine and theophylline, which are known to affect the Ca2+ channels responsible for Ca(2+)-induced Ca2+ release (CICR) in excitable cells. The results obtained essentially indicate (a) that neither ryanodine nor ruthenium red affects the generation of periodic K(Ca2+) current pulses in whole-cell experiments, and (b) that histamine-induced Ca2+ oscillations are inhibited by caffeine and theophylline in a dose-dependent manner. However, these methylxanthines were unable, at concentrations ranging from 0.1 mM to 10 mM, either to mobilize Ca2+ from internal stores or to block the initial Ca2+ rise evoked by histamine. In addition, both methylxanthines showed at high concentrations (10-20 mM) a moderate inhibitory action on the production of InsP3 induced by histamine. This effect was not essential to the action of caffeine on the oscillatory release of Ca2+, since an inhibition by caffeine of InsP3-induced Ca2+ oscillations was still observed in whole-cell experiments where the InsP3 concentration was kept constant. The results also show (c) that the application of either caffeine or theophylline during histamine stimulation leads systematically to an increased Ca2+ sequestration in InsP3-sensitive Ca2+ pools, the effect observed with theophylline being stronger than that resulting from the application of caffeine, and finally (d) that the action of caffeine and theophylline is not related to an increase in cAMP concentration since neither forskolin (10-50 microM) nor 8-Br-cAMP (1 mM) caused an inhibition of the InsP3-induced Ca2+ oscillations. It is concluded on the basis of these results that the agonist-evoked Ca2+ oscillations in HeLa cells do not involve directly or indirectly a ryanodine-sensitive Ca(2+)-release channel with CICR properties, but rather arise from a control by Ca2+ of the InsP3 Ca(2+)-release process.

Plasma albumin induces calcium waves in rat cortical astrocytes

“…Ryanodine has no significant effect on either the rate of rise of calcium spikes or on the spike frequency, suggesting that Ca-dependent Ca release plays little role in the production of calcium spikes in astrocytes. Similar results have been obtained in other calcium spiking cells such as HeLa cells (Diarra et al, 1994) and pituitary gonadotrophs (Stojilkovic et al, 1994).…”

Simultaneous presence of cAMP and cGMP exert a co-ordinated inhibitory effect on the agonist-evoked Ca2+ signal in pancreatic acinar cells

“…Our initial demonstration of the inhibition of the Cat response by caffeine has been confirmed in various other tissues [5,11,17,27,30]. Regarding the mechanism through which caffeine exerts its effect, a key point is the reproducibility of this effect by other non-specific PDE inhibitors, including those chemically unrelated to the methylxanthines, suggesting that an increase in cAMP and/or cGMP could be involved.…”

Spatially restricted subcellular Ca2+ signaling downstream of store-operated calcium entry encoded by a cortical tunneling mechanism

“…In Xenopus oocytes Ca 2+ tunneling is particularly effective at stimulating Ca 2+ -activated Cl channels at the PM 7 . Therefore, to test whether Ca 2+ -dependent PM localized effectors respond to Ca 2+ tunneling, we turned to Ca 2+ -activated K + channels (K Ca ), which are expressed in HeLa cells 29 . Histamine-dependent Ca 2+ release when stores are full induces a transient K Ca current (Fig.…”