Article
Cardiac & Cardiovascular Systems
Jinhong Wei, Wenting Guo, Ruiwu Wang, John Paul Estillore, Darrell Belke, Yong-Xiang Chen, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, S. R. Wayne Chen
Summary: The physiological significance of PKA phosphorylation of RyR2 in the heart is still poorly understood. Recent structural studies have shown that the PKA phosphorylation site S2030 in RyR2 is located within a pathway that is important for the termination of Ca2+ release. We investigated the impact of S2030 mutations on Ca2+ release termination in cells and generated a mouse model to study the role of S2030 in a physiological setting.
CIRCULATION RESEARCH
(2023)
Article
Plant Sciences
Katherine E. Helliwell, Friedrich H. Kleiner, Hayley Hardstaff, Abdul Chrachri, Trupti Gaikwad, Deborah Salmon, Nicholas Smirnoff, Glen L. Wheeler, Colin Brownlee
Summary: Diatoms are globally important phytoplankton that dominate coastal and polar-ice assemblages. They employ Ca2+ signaling to respond to osmotic stress and regulate cell volume.
Article
Biology
S. J. Richardson, C. G. Thekkedam, M. G. Casarotto, N. A. Beard, A. F. Dulhunty
Summary: Cardiac ryanodine receptors (RyR2) play a crucial role in releasing intracellular calcium essential for cardiac myocyte contraction. The regulation of ion channel opening by intracellular factors, including FK506 binding proteins FKBP12 and FKBP12.6, and their impact on RyR2 activity and cardiac contraction are still debated. This study demonstrates that FKBP12 activates RyR2 with high affinity and inhibits RyR2 with lower affinity, suggesting a model of negative cooperativity in FKBP12 binding. The dissociation of FKBP12/12.6 could dynamically affect RyR2 activity, indicating the significant role of FKBP12/12.6 in Ca2+ signaling and cardiac function.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Chris Lindsay, Maria Musgaard, Angela J. Russell, Rebecca Sitsapesan
Summary: This study found that all the statins examined could activate RyR1, and cerivastatin was the most potent in activating RyR1, supporting the hypothesis that RyR1 activation is implicated in statin-induced myopathy. Several statin analogues were identified that retained HMG-CoA reductase inhibition but lacked the ability to modulate RyR1.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alexander Maltsev, Edward Evdokimovskii, Yury M. Kokoz
Summary: Protein kinase C is a superfamily of intracellular effector molecules that play crucial roles in controlling cellular functions. This study identified a wide expression of PKC transcripts in left ventricular myocytes, with PKC activity tonically regulating various cellular processes, including voltage-gated Ca2+ currents and nitric oxide production. The findings suggest that PKC-mediated Ca2+ signaling may play a significant role in the development of cardiovascular pathologies and myocardial plasticity at the cardiomyocyte level.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Physiology
Jose Millet, Yuriana Aguilar-Sanchez, Dmytro Kornyeyev, Maedeh Bazmi, Diego Fainstein, Julio A. Copello, Ariel L. Escobar
Summary: Ca2+ alternans (Ca-Alts) are beat-to-beat changes in the amplitude of Ca2+ transients that frequently occur during tachycardia, ischemia, or hypothermia. This alternation appears to result from variation in Ca2+ release from the sarcoplasmic reticulum (SR) in consecutive heartbeats, possibly due to changes in action potential duration, delayed recovery of RYR Ca2+ release channel (RYR2) inactivation, or incomplete Ca2+ refilling of the SR. Using fluorescence local field optical mapping (FLOM), researchers observed larger Ca-Alts in colder regions without changes in action potential duration. The findings suggest that the steep temperature dependency of Ca-Alts during tachycardia may be related to insufficient SERCA-mediated Ca2+ uptake into the SR, which can be promoted by partial pharmacologic inhibition of SERCA2a.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Physiology
Valeriy Lukyanenko, Joaquin Muriel, Daniel Garman, Leonid Breydo, Robert J. Bloch
Summary: Dysferlin-null myofibers generate abnormal Ca2+ transients, which can be suppressed by a permeable Ca2+ chelator, BAPTA-AM. Dysferlin's C2A domain protects muscle against injury by binding Ca2+ and suppressing abnormal Ca2+ signaling.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Paschou, Danai Liaropoulou, Vasileia Kalaitzaki, Spiros Efthimiopoulos, Panagiota Papazafiri
Summary: In this study, the downregulation of APP in SH-SY5Y cells altered the expression of ion channels and signaling proteins involved in synaptic and Ca2+ signaling. The levels of GluR2 and GluR4 subunits of AMPAR were increased, as well as the expression of ER-residing proteins. Changes in phosphorylation states of AKT, PP2A, CaMKIV, GSK, ERK1/2, CaMKII, and CREB were observed, indicating an interconnection between Ca2+ signaling from the plasma membrane and ER to the nucleus. Interestingly, reduced responses to physiological stimuli, particularly in mobilizing Ca2+ from the ER, were detected in APP knockdown cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Noushin Ahmadpour, Meher Kantroo, Jillian L. Stobart
Summary: Astrocytes play crucial roles in the brain by modulating microdomain calcium events, which are diverse and complex in nature. These events are regulated by different signaling mechanisms and can impact synaptic activity, blood flow, and even behaviors. Rapid microdomain calcium events in astrocytes are linked to local neuronal circuit activity, highlighting their importance in brain function.
Review
Biochemistry & Molecular Biology
Maryam Al-Khannaq, Jonathan Lytton
Summary: Potassium-dependent sodium-calcium exchangers (NCKX) play a crucial role in regulating calcium signaling and homeostasis, especially in cells and tissues with fluctuating ion concentrations. NCKX transporters can be modulated through various mechanisms, including changes in cellular location, protein expression, genetic alterations, substrate concentration, and post-translational modifications. Understanding the regulation of NCKX has the potential to provide valuable insights into transporter function and the treatment of dysregulated calcium homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
E. A. Rog-Zielinska, R. Moss, W. Kaltenbacher, J. Greiner, P. Verkade, G. Seemann, P. Kohl, M. B. Cannell
Summary: Detailed knowledge of the ultrastructure of intracellular compartments is essential for understanding cell function, particularly in cardiac muscle cells where the close apposition of transverse-tubule (TT) and sarcoplasmic reticulum (SR) membranes supports excitation-contraction coupling. Using ultra-rapid high-pressure freezing and electron microscopy, the study compared the fine structure of TT and SR in rabbit and mouse ventricular cardiomyocytes. The results suggest that HPF-preserved samples exhibit larger SR terminal cisternae and provide novel insights into the cardiac physiology of TT and SR ultrastructure.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Medicine, Research & Experimental
Xiao-Qiang Li, Yun-Min Zheng, Jorge Reyes-Garcia, Yong-Xiao Wang
Summary: The study revealed the distinct roles of RyR1 in systemic and pulmonary artery smooth muscle cells, providing clear genetic evidence for their functional importance in muscle contraction and Ca2+ release.
Article
Medicine, Research & Experimental
Maarten A. J. De Smet, Alessio Lissoni, Timur Nezlobinsky, Nan Wang, Eef Dries, Marta Perez-Hernandez, Xianming Lin, Matthew Amoni, Tim Vervliet, Katja Witschas, Eli Rothenberg, Geert Bultynck, Rainer Schulz, Alexander V. Panfilov, Mario Delmar, Karin R. Sipido, Luc Leybaert
Summary: Cx43 hemichannels are activated during diastolic Ca2+ release in ventricular cardiomyocytes, contributing to enhanced Ca2+ dynamics due to Ca2+ entry and coupling to release microdomains. Hemichannel opening also leads to delayed afterdepolarizations and triggered action potentials. Increased hemichannel activity is associated with electrical instability in failing human hearts compared to nonfailing donor hearts, suggesting a potentially novel mechanism of cardiac arrhythmogenesis in heart failure.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Pharmacology & Pharmacy
Katsuharu Tsuchida, Hitomi Hirose, Sachiyo Ozawa, Haruka Ishida, Tomomi Iwatani, Uraka Matsumoto
Summary: Monensin shortened action potential duration and reduced plateau phase amplitude in ventricular myocytes primarily by decreasing L-type calcium current, activating reverse mode of Na-Ca exchange current, and increasing Na-K pump current, and secondarily by decreasing sodium current. Inward rectifying K current and delayed outward K current were minimally affected by monensin-induced changes. Elevation of intracellular Na can have multiple influences on electrophysiological phenomena in cardiac myocytes.
Article
Cell Biology
Camille S. Wang, Lisa M. Monteggia, Ege T. Kavalali
Summary: Calcium (Ca2+) signaling is tightly regulated within a presynaptic bouton, involving evoked, spontaneous, and baseline signals derived from multiple sources. These signals have non-overlapping domains within the synapse and interact through synaptic vesicle turnover.
Article
Parasitology
Elizabeth Valdivieso, Fabiola Mejias, Carlos Torrealba, Gustavo Benaim, Vladimir V. Kouznetsov, Felipe Sojo, Fernando A. Rojas-Ruiz, Francisco Arvelo, Francehuli Dagger
Article
Biochemistry & Molecular Biology
Sheerly Rodriguez, May-Li Silva, Gustavo Benaim, Jose Bubis
Article
Parasitology
Andrea Pinto-Martinez, Vanessa Hernandez-Rodriguez, Jessica Rodriguez-Duran, Elzbieta Hejchman, Gustavo Benaim
EXPERIMENTAL PARASITOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Jose Ruben Ramirez-Iglesias, Maria Carolina Perez-Gordones, Jesus Rafael del Castillo, Alfredo Mijares, Gustavo Benaim, Marta Mendoza
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2018)
Article
Pathology
Parnian Ahmadi Moghaddam, Rajesh Singh, Mandana Mahmoodi, Meenakshi Mehrotra, Gustavo Benaim, Rajyalakshmi Luthra, Alberto Paniz-Mondolfi
PATHOLOGY RESEARCH AND PRACTICE
(2018)
Review
Infectious Diseases
Maria E. Grillet, Juan V. Hernandez-Villena, Martin S. Llewellyn, Alberto E. Paniz-Mondolfi, Adriana Tami, Maria F. Vincenti-Gonzalez, Marilianna Marquez, Adriana C. Mogollon-Mendoza, Carlos E. Hernandez-Pereira, Juan D. Plaza-Morr, Gabriella Blohm, Mario J. Grijalva, Jaime A. Costales, Heather M. Ferguson, Philipp Schwabl, Luis E. Hernandez-Castro, Poppy H. L. Lamberton, Daniel G. Streicker, Daniel T. Haydon, Michael A. Miles, Alvaro Acosta-Serrano, Harry Acquattela, Maria G. Basanez, Gustavo Benaim, Luis A. Colmenares, Jan E. Conn, Raul Espinoza, Hector Freilij, Mary C. Graterol-Gil, Peter J. Hotez, Hirotomo Kato, John A. Lednicky, Clara E. Martinez, Santiago Mas-Coma, J. Glen Morris, Juan C. Navarro, Jose L. Ramirez, Marlenes Rodriguez, Julio A. Urbina, Leopoldo Villegas, Maikell J. Segovia, Hernan J. Carrasco, James L. Crainey, Sergio L. B. Luz, Juan D. Moreno, Oscar O. Noya Gonzalez, Juan D. Ramirez, Belkisyole Alarcon-de Noya
LANCET INFECTIOUS DISEASES
(2019)
Article
Biochemistry & Molecular Biology
Jessica Rodriguez-Duran, Andrea Pinto-Martinez, Cecilia Castillo, Gustavo Benaim
Article
Parasitology
Nathalia Martinez-Sotillo, Andrea Pinto-Martinez, Elibieta Hejchman, Gustavo Benaim
PARASITOLOGY INTERNATIONAL
(2019)
Article
Veterinary Sciences
Roy Madigan, Sean Majoy, Kristine Ritter, Juan Luis Concepcion, Maria Elizabeth Marquez, Sasha Caribay Silva, Chih-Ling Zao, Alexandra Perez Alvarez, Alfonso J. Rodriguez-Morales, Adriana C. Mogollon-Mendoza, J. Scot Estep, Gustavo Benaim, Alberto E. Paniz-Mondolfi
JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
(2019)
Article
Parasitology
Zain Gil, Nathalia Martinez-Sotillo, Andrea Pinto-Martinez, Fabiola Mejias, Juan Carlos Martinez, Ivan Galindo, Eric Oldfield, Gustavo Benaim
PARASITOLOGY RESEARCH
(2020)
Review
Immunology
Gustavo Benaim, Alberto E. Paniz-Mondolfi, Emilia Mia Sordillo, Nathalia Martinez-Sotillo
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2020)
Review
Pharmacology & Pharmacy
Gustavo Benaim, Alberto E. Paniz-Mondolfi, Emilia Mia Sordillo
Summary: Repurposing approved drugs for neglected diseases is a accepted strategy, with amiodarone showing promising trypanocidal and leishmanicidal activity through multiple mechanisms.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Biochemistry & Molecular Biology
Maria C. Perez-Gordones, Jose R. Ramirez-Iglesias, Gustavo Benaim, Marta Mendoza
Summary: The Trypanosomatidae family includes unicellular organisms responsible for tropical diseases in humans and animals. Among these, livestock tripanosomosis caused by Trypanosoma brucei brucei, Trypanosoma equiperdum, and Trypanosoma evansi have a significant impact on animal protein productivity. In this study, the presence of a store-operated Ca2+-entry (SOCE) in T. equiperdum was demonstrated, likely mediated by putative transient receptor potential (TRP) channels.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2021)
Article
Biology
Andre Rey-Cibati, Mariana Valladares-Delgado, Gustavo Benaim
Article
Microbiology
Andrea K. Pinto-Martinez, Jessica Rodriguez-Duran, Xenon Serrano-Martin, Vanessa Hernandez-Rodriguez, Gustavo Benaim
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2018)