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Structure and Properties of Proteins Involved in Ca2+ Transport and Homeostasis 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Macromolecules".

Deadline for manuscript submissions: closed (10 December 2022) | Viewed by 12781

Special Issue Editors

1. Department of Biomedical Sciences, University of Padova, Padova, Italy
2. Padova Neuroscience Center (PNC), University of Padova, Padova, Italy
Interests: organelle contact sites; mitochondria; calcium signaling; genetically encoded sensors; neurodegenerative diseases; endoplasmic reticulum; plasma membrane calcium pumps
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is difficult to underestimate the role of Ca2+ in the cell functioning since calcium ions play a fundamental role in many cellular processes. Ca2+ actively participates in a variety of cell signaling pathways by binding to several calcium-binding proteins. Calcium transport in and out of the cell membrane is strictly regulated through the use of pumps and channels and, once inside the cell, Ca2+ is stored in specific compartments or bound to specific proteins that keep its free concentration at the proper value. The structure of most of the proteins involved in calcium transport and homeostasis is currently known, and their functioning mechanism has been partially clarified. The goal of this Special Issue is to produce an up-to-date summary of the present knowledge of the structure–function relationship of the proteins involved in this process.

We encourage the submission of both original research articles and topical reviews on proteins involved in Ca2+ transport and homeostasis.

Prof. Dr. Giuseppe Zanotti
Dr. Tito Calì
Guest Editors

Manuscript Submission Information

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Keywords

  • calcium transport
  • calcium-binding proteins
  • calcium homeostasis
  • calcium pumps
  • Ca2+-ATPases
  • calcium cell signaling pathways
  • sarcoplasmic reticulum
  • calsequestrin
  • calmodulin
  • calbindins

Related Special Issue

Published Papers (4 papers)

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Research

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17 pages, 4401 KiB  
Article
Zingerone Modulates Neuronal Voltage-Gated Na+ and L-Type Ca2+ Currents
by Ming-Chi Lai, Sheng-Nan Wu and Chin-Wei Huang
Int. J. Mol. Sci. 2022, 23(6), 3123; https://doi.org/10.3390/ijms23063123 - 14 Mar 2022
Cited by 7 | Viewed by 1899
Abstract
Zingerone (ZO), a nontoxic methoxyphenol, has been demonstrated to exert various important biological effects. However, its action on varying types of ionic currents and how they concert in neuronal cells remain incompletely understood. With the aid of patch clamp technology, we investigated the [...] Read more.
Zingerone (ZO), a nontoxic methoxyphenol, has been demonstrated to exert various important biological effects. However, its action on varying types of ionic currents and how they concert in neuronal cells remain incompletely understood. With the aid of patch clamp technology, we investigated the effects of ZO on the amplitude, gating, and hysteresis of plasmalemmal ionic currents from both pituitary tumor (GH3) cells and hippocampal (mHippoE-14) neurons. The exposure of the GH3 cells to ZO differentially diminished the peak and late components of the INa. Using a double ramp pulse, the amplitude of the INa(P) was measured, and the appearance of a hysteresis loop was observed. Moreover, ZO reversed the tefluthrin-mediated augmentation of the hysteretic strength of the INa(P) and led to a reduction in the ICa,L. As a double ramp pulse was applied, two types of voltage-dependent hysteresis loops were identified in the ICa,L, and the replacement with BaCl2-attenuated hysteresis of the ICa,L enhanced the ICa,L amplitude along with the current amplitude (i.e., the IBa). The hysteretic magnitude of the ICa,L activated by the double pulse was attenuated by ZO. The peak and late INa in the hippocampal mHippoE-14 neurons was also differentially inhibited by ZO. In addition to acting on the production of reactive oxygen species, ZO produced effects on multiple ionic currents demonstrated herein that, considered together, may significantly impact the functional activities of neuronal cells. Full article
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18 pages, 3203 KiB  
Article
Evidence for Inhibitory Perturbations on the Amplitude, Gating, and Hysteresis of A-Type Potassium Current, Produced by Lacosamide, a Functionalized Amino Acid with Anticonvulsant Properties
by Hsin-Yen Cho, Tzu-Hsien Chuang and Sheng-Nan Wu
Int. J. Mol. Sci. 2022, 23(3), 1171; https://doi.org/10.3390/ijms23031171 - 21 Jan 2022
Cited by 2 | Viewed by 1736
Abstract
Lacosamide (Vimpat®, LCS) is widely known as a functionalized amino acid with promising anti-convulsant properties; however, adverse events during its use have gradually appeared. Despite its inhibitory effect on voltage-gated Na+ current (INa), the modifications on varying [...] Read more.
Lacosamide (Vimpat®, LCS) is widely known as a functionalized amino acid with promising anti-convulsant properties; however, adverse events during its use have gradually appeared. Despite its inhibitory effect on voltage-gated Na+ current (INa), the modifications on varying types of ionic currents caused by this drug remain largely unexplored. In pituitary tumor (GH3) cells, we found that the presence of LCS concentration-dependently decreased the amplitude of A-type K+ current (IK(A)) elicited in response to membrane depolarization. The IK(A) amplitude in these cells was sensitive to attenuation by the application of 4-aminopyridine, 4-aminopyridine-3-methanol, or capsaicin but not by that of tetraethylammonium chloride. The effective IC50 value required for its reduction in peak or sustained IK(A) was calculated to be 102 or 42 µM, respectively, while the value of the dissociation constant (KD) estimated from the slow component in IK(A) inactivation at varying LCS concentrations was 52 µM. By use of two-step voltage protocol, the presence of this drug resulted in a rightward shift in the steady-state inactivation curve of IK(A) as well as in a slowing in the recovery time course of the current block; however, no change in the gating charge of the inactivation curve was detected in its presence. Moreover, the LCS addition led to an attenuation in the degree of voltage-dependent hysteresis for IK(A) elicitation by long-duration triangular ramp voltage commands. Likewise, the IK(A) identified in mouse mHippoE-14 neurons was also sensitive to block by LCS, coincident with an elevation in the current inactivation rate. Collectively, apart from its canonical action on INa inhibition, LCS was effective at altering the amplitude, gating, and hysteresis of IK(A) in excitable cells. The modulatory actions on IK(A), caused by LCS, could interfere with the functional activities of electrically excitable cells (e.g., pituitary tumor cells or hippocampal neurons). Full article
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Review

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25 pages, 2373 KiB  
Review
Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System
by Ghassan Bkaily and Danielle Jacques
Int. J. Mol. Sci. 2023, 24(10), 8803; https://doi.org/10.3390/ijms24108803 - 15 May 2023
Cited by 6 | Viewed by 2882
Abstract
Calcium is a highly positively charged ionic species. It regulates all cell types’ functions and is an important second messenger that controls and triggers several mechanisms, including membrane stabilization, permeability, contraction, secretion, mitosis, intercellular communications, and in the activation of kinases and gene [...] Read more.
Calcium is a highly positively charged ionic species. It regulates all cell types’ functions and is an important second messenger that controls and triggers several mechanisms, including membrane stabilization, permeability, contraction, secretion, mitosis, intercellular communications, and in the activation of kinases and gene expression. Therefore, controlling calcium transport and its intracellular homeostasis in physiology leads to the healthy functioning of the biological system. However, abnormal extracellular and intracellular calcium homeostasis leads to cardiovascular, skeletal, immune, secretory diseases, and cancer. Therefore, the pharmacological control of calcium influx directly via calcium channels and exchangers and its outflow via calcium pumps and uptake by the ER/SR are crucial in treating calcium transport remodeling in pathology. Here, we mainly focused on selective calcium transporters and blockers in the cardiovascular system. Full article
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19 pages, 2065 KiB  
Review
Calcium Signalling in Heart and Vessels: Role of Calmodulin and Downstream Calmodulin-Dependent Protein Kinases
by Sofia Beghi, Malgorzata Furmanik, Armand Jaminon, Rogier Veltrop, Nikolas Rapp, Kanin Wichapong, Elham Bidar, Annamaria Buschini and Leon J. Schurgers
Int. J. Mol. Sci. 2022, 23(24), 16139; https://doi.org/10.3390/ijms232416139 - 17 Dec 2022
Cited by 8 | Viewed by 5637
Abstract
Cardiovascular disease is the major cause of death worldwide. The success of medication and other preventive measures introduced in the last century have not yet halted the epidemic of cardiovascular disease. Although the molecular mechanisms of the pathophysiology of the heart and vessels [...] Read more.
Cardiovascular disease is the major cause of death worldwide. The success of medication and other preventive measures introduced in the last century have not yet halted the epidemic of cardiovascular disease. Although the molecular mechanisms of the pathophysiology of the heart and vessels have been extensively studied, the burden of ischemic cardiovascular conditions has risen to become a top cause of morbidity and mortality. Calcium has important functions in the cardiovascular system. Calcium is involved in the mechanism of excitation–contraction coupling that regulates numerous events, ranging from the production of action potentials to the contraction of cardiomyocytes and vascular smooth muscle cells. Both in the heart and vessels, the rise of intracellular calcium is sensed by calmodulin, a protein that regulates and activates downstream kinases involved in regulating calcium signalling. Among them is the calcium calmodulin kinase family, which is involved in the regulation of cardiac functions. In this review, we present the current literature regarding the role of calcium/calmodulin pathways in the heart and vessels with the aim to summarize our mechanistic understanding of this process and to open novel avenues for research. Full article
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