Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

Role of Protons in Calcium Signaling

Version 1 : Received: 16 March 2020 / Approved: 17 March 2020 / Online: 17 March 2020 (09:14:03 CET)
Version 2 : Received: 30 April 2020 / Approved: 2 May 2020 / Online: 2 May 2020 (16:40:16 CEST)

How to cite: Molinari, G.; Nervo, E. Role of Protons in Calcium Signaling. Preprints 2020, 2020030274. Molinari, G.; Nervo, E. Role of Protons in Calcium Signaling. Preprints 2020, 2020030274.


36 years after the publication of the important article by Busa and Nuccitelli on the variability of intracellular pH (pHi) and the interdependence of pHi and intracellular Ca2+ concentration ([Ca2+]i), little research has been carried out on pHi and calcium signaling. Moreover, the results appear to be contradictory. Some authors claim that the increase in [Ca2+]i is due to a reduction in pHi, others that it is caused by an increase in pHi. The reasons for these conflicting results have not yet been discussed and clarified in an exhaustive manner. Variations in pHi have a significant impact on the increase in [Ca2+]i and hence on some of the basic biochemical mechanisms of calcium signaling. This paper focuses on the possible triggering role of protons, highlighting the mechanisms potentially involved and the open issues that could be clarified by research.


Ca-signaling; IP3; RyR; intracellular-pH; [Ca2+]i; proton.


Biology and Life Sciences, Cell and Developmental Biology

Comments (1)

Comment 1
Received: 2 May 2020
Commenter: Giuliano Molinari
Commenter's Conflict of Interests: Author
Comment: ver 2, 30 April 2020; details of most important changes: Keywords: 3 substitutions Section 4: the central part, from line 319 (Subsequently the IP3 activates..) to line 407 (In summary, the action of IP3..), replaces and extends the previous central part, suggesting an allosteric modulation of IP3R by protons and the names of five possible candidate 5-phosphatases for the release of protons from IP3. Further, at ending, lines 443-447 are added, with deductions from the comparison between the neutralization rate and the diffusion rate of protons. Section 5: at ending, lines 505-510 are added with the concept of Ca2+ oscillations as consequence of parallel, underlying proton oscillations. Section 6: at ending, lines 549 and 550 are added. References: 4 deleted, 67 added.
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