Modulation of endoplasmic reticulum Ca2+ store filling by cyclic ADP-ribose promotes inositol trisphosphate (IP3)-evoked Ca2+ signals.

Journal article

In addition to its well established function in activating Ca(2+) release from the endoplasmic reticulum (ER) through ryanodine receptors (RyR), the second messenger cyclic ADP-ribose (cADPR) also accelerates the activity of SERCA pumps, which sequester Ca(2+) into the ER. Here, we demonstrate a potential physiological role for cADPR in modulating cellular Ca(2+) signals via changes in ER Ca(2+) store content, by imaging Ca(2+) liberation through inositol trisphosphate receptors (IP(3)R) in Xenopus oocytes, which lack RyR. Oocytes were injected with the non-metabolizable analog 3-deaza-cADPR, and cytosolic [Ca(2+)] was transiently elevated by applying voltage-clamp pulses to induce Ca(2+) influx through expressed plasmalemmal nicotinic channels. We observed a subsequent potentiation of global Ca(2+) signals evoked by strong photorelease of IP(3), and increased numbers of local Ca(2+) puffs evoked by weaker photorelease. These effects were not evident with cADPR alone or following cytosolic Ca(2+) elevation alone, indicating that they did not arise through direct actions of cADPR or Ca(2+) on the IP(3)R, but likely resulted from enhanced ER store filling. Moreover, the appearance of a new population of puffs with longer latencies, prolonged durations, and attenuated amplitudes suggests that luminal ER Ca(2+) may modulate IP(3)R function, in addition to simply determining the size of the available store and the electrochemical driving force for release.

Authors: Yamasaki-Mann, M; Demuro, A; Parker, I

• Journal: Journal of biological chemistry
• Volume: 285
• Issue: 32
• Pages: 25053-25061
• Publication date: 2010-08-01
• DOI: 10.1074/jbc.m109.095257
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Cytosol; Electrochemistry; Xenopus laevis; Kinetics; Ryanodine Receptor Calcium Release Channel; Cyclic ADP-Ribose; Oocytes; Calcium Signaling; Inositol 1,4,5-Trisphosphate; Models, Biological; Endoplasmic Reticulum; Animals; Patch-Clamp Techniques; Time Factors; Calcium