Modulation of endoplasmic reticulum Ca2+ store filling by cyclic ADP-ribose promotes inositol trisphosphate (IP3)-evoked Ca2+ signals.
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.
Yamasaki-Mann
Michiko
M
Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA. michikomann@ucla.edu
Demuro
Angelo
A
Parker
Ian
I
D000818:Animals; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D020013:Calcium Signaling; D036563:Cyclic ADP-Ribose / Q000737:chemistry*; D003600:Cytosol / Q000378:metabolism; D004563:Electrochemistry / Q000379:methods; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000737:chemistry*; D007700:Kinetics; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry; D013997:Time Factors; D014982:Xenopus laevis
D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium