Activation of Ca(2+)-dependent currents in cultured rat dorsal root ganglion neurones by a sperm factor and cyclic ADP-ribose.

Abstract

The effects of intracellular application of two novel Ca2' releasing agents have been studied in cultured rat dorsal root ganglion (DRG) neurones by monitoring Ca2+-dependent currents as a physiological index of raised free cytosolic Ca21 ([Ca21] ). A protein based sperm factor (SF) extracted from mammalian sperm, has been found to trigger Ca21 oscillations and to sensitize unfertilized mammalian eggs to calcium induced calcium release (CICR). In this study intracellular application of SF activated Ca2+-dependent currents in approximately two-thirds of DRG neurones. The SF induced activity was abolished by heat treatment, attenuated by increasing the intracellular Ca2' buffering capacity of the cells and persisted when extracellular Ca2+ was replaced by Ba2 . In addition, activity could be triggered or potentiated by loading the cells with Ca2' by activating a series of voltage-gated Ca21 currents. Ca2+-activated inward current activity was also generated by intracellular application of cyclic ADP-ribose (cADPR), a metabolite of NAD+, which causes Ca21 release in sea urchin eggs. This activity could also be enhanced by loading the cells with Ca2+. The cADPR induced activity, but not the SF induced activity, was abolished by depleting the caffeine sensitive Ca21 store. Ruthenium red markedly attenuated SF induced activity but had little action on cADPR induced activity or caffeine induced activity. Our results indicate that both SF and cADPR release intracellular Ca21 pools in DRG neurones and that they appear to act on subtly distinct stores or distinct intracellular Ca2' release mechanisms, possibly by modulating CICR.

An Antagonist of cADP-ribose Inhibits Arrhythmogenic Oscillations of Intracellular Ca2+ In Heart Cells

“…ADP-ribosyl cyclase activity has been identified in rat cardiac myocytes (7), and intracellular levels of cADPR have been estimated to be of the order of 200 nM (11). Furthermore, cADPR has been reported to enhance CICR in a number of preparations, including guinea pig heart cells (12), sea urchin eggs (33,34), and neuronal cells (5,(35)(36)(37). This would support the hypothesis that suppression of Ca 2ϩ oscillations (provoked by isoproterenol and ouabain) by 8-amino-cADPR and 8-bromo-cADPR is because of antagonism of the actions of endogenous cADPR, which sensitizes the CICR mechanism to Ca 2ϩ .…”

Extracellular Synthesis of cADP-Ribose from Nicotinamide-Adenine Dinucleotide by Rat Cortical Astrocytes in Culture

“…Increasing pharmacological evidence has implicated cADPR in the calcium-induced calcium-release process (CICR) and in the modulation of the activity of the ryanodine receptor (Galione et al, 1991;Currie et al, 1992;Meszaros et al, 1993;Lee et al, 1994). cADPR has been shown to induce calcium release in permeabilized rat pituitary cells (Koshiyama et al, 1991), rat brain microsomes , heart sarcoplasmic reticulum vesicles (Meszaros et al, 1993), and rat pancreatic cell microsomes (Takasawa et al, 1993a), as well as in electrophysiological studies in intact rat dorsal root ganglion neurons (Currie et al, 1992) and in cultured bullfrog sympathetic neurons (Hua et al, 1994), in which cADPR appeared to mediate calcium oscillations produced by CICR through the ryanodine receptor. In sea urchin egg microsomes, the formation of cADPR from NAD and subsequent calcium release is enhanced by cGMP .…”

Cyclic aristeromycin diphosphate ribose: A potent and poorly hydrolysable Ca2+‐mobilising mimic of cyclic adenosine diphosphate ribose

“…2) [1], it is known to be more effective than, and to work independently of, inositol 1,4,5-trisphosphate in mobilising internal stores of calcium in sea urchin eggs [2]. Since its discovery in 1987 [3], cADPR has been shown to be present and active in a wide variety of mammalian and invertebrate tissue [4][5][6] and its cyclic structure has been confirmed by X-ray crystallography [7]. The metabolic pathway of cADPR is known ( Fig.…”