Caffeine-induced inhibition of inositol(1,4,5)-trisphosphate-gated calcium channels from cerebellum.

Abstract

Effects of the xanthine drug caffeine on inositol (1,4,5)-trisphosphate (InsP3)-gated calcium (Ca) channels from canine cerebellum were studied using single channels incorporated into planar lipid bilayers. Caffeine, used widely as an agonist of ryanodine receptors, inhibited the activity of InsP3-gated Ca channels in a noncooperative fashion with halfinhibition at 1.64 mM caffeine. The frequency of channel openings was decreased more than threefold after addition of 5 mM caffeine; there was only a small effect on mean open time of the channels, and the single channel conductance was unchanged. Increased InsP3 concentration overcame the inhibitory action of caffeine, but caffeine did not reduce specific [3H]InsP3 binding to the receptor. The inhibitory action of caffeine on InsP3 receptors suggests that the action of caffeine on the intracellular Ca pool must be interpreted with caution when both ryanodine receptors and InsP3 receptors are present in the cell.

Inositol 1,4,5‐trisphosphate receptors and neurodegenerative disorders

“…This alleviated the pathological phenotype in SCA2 mice, reduced neuronal cell death and improved motor coordination [90]. Moreover, IICR might be pharmacologically blocked with caffeine [122] and by therapeutic levels of lithium in the presence of neuronal calcium sensor-1 [123]. There are several other potential approaches to inhibit IICR in the context of neurodegeneration.…”

Ryanodine-Sensitive Component of Calcium Transients Evoked by Nerve Firing at Presynaptic Nerve Terminals

“…Caffeine has been much used in various tissue for the sole purpose of detecting the involvement of Ca 2ϩ release through the ryanodine channels (for review, see Tsien and Tsien, 1990). Recent results suggest that this simple interpretation of the effects of caffeine is not always justified (Bezprozvanny et al, 1994;Hoffer and Machen, 1994).…”

“…12 B and Besides its well known effects on the ryanodine-sensitive channels, caffeine was reported recently to reduce intracellular [Ca 2ϩ ] in epithelial cells and to promote Ca 2ϩ sequestration into an IP 3 -insensitive store (Hoffer and Machen, 1994). Caffeine also blocked the IP 3 -activated Ca 2ϩ release channels isolated from the cerebellum tissue (Bezprozvanny et al, 1994). Thus, there are at least two possible mechanisms whereby caffeine can reduce [Ca 2ϩ ] i .…”

Activation of Metabotropic Glutamate Receptors Induces Periodic Burst Firing and Concomitant Cytosolic Ca2+Oscillations in Cerebellar Interneurons

“…To further test the involvement of InsP 3 Rs, responses to quisqualate were analyzed before and after the addition of caffeine (10 mM) to the bath. At this concentration, caffeine will inhibit InsP 3 Rs and can also activate ryanodine receptors (RyRs) (Bezprozvanny et al, 1994;Hernández-Cruz et al, 1997;Zucchi and Ronca-Testoni, 1997). We observed caffeine-induced Ca 2ϩ transients, presumably caused by RyR activation, in only 1 of 10 MLIs.…”