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Article: A Toxic Sterolysin From a 1950s Culture of Gymnodinium Veneficum Ballantine.

Place, Allen R / Ramos-Franco, Josefina / Waters, Amanda L / Hamann, Mark T

Research square

2024

Abstract: In 1957 Abbott and Ballentine described a highly toxic activity from a dinoflagellate isolated from the English Channel. in 1949 by Mary Park. From a culture maintained at Plymouth Laboratory since 1950, we have been able to isolate two toxic molecules ( ... ...

Abstract	In 1957 Abbott and Ballentine described a highly toxic activity from a dinoflagellate isolated from the English Channel. in 1949 by Mary Park. From a culture maintained at Plymouth Laboratory since 1950, we have been able to isolate two toxic molecules (Abbotoxin and 59-E-Chloro-Abbotoxin), determine the planar structures by analysis of HRMS and 1D and 2D NMR spectra and found them to be karlotoxin (KmTx) congeners. Both toxins kill larval zebrafish with symptoms identical to that described by Abbot and Ballantine for gobies (
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3970188/v1
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Article ; Online: Approaching ryanodine receptor therapeutics from the calcin angle.

Ramos-Franco, Josefina / Fill, Michael

The Journal of general physiology

2016 Volume 147, Issue 5, Page(s) 369–373

MeSH term(s)	Animals ; Calcium/metabolism ; Calcium Signaling/drug effects ; Calcium Signaling/physiology ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Humans ; Peptides/chemistry ; Peptides/metabolism ; Peptides/pharmacology ; Ryanodine Receptor Calcium Release Channel/metabolism ; Scorpion Venoms/chemistry
Chemical Substances	Peptides ; Ryanodine Receptor Calcium Release Channel ; Scorpion Venoms ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2016-04-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3118-5
ISSN	1540-7748 ; 0022-1295
ISSN (online)	1540-7748
ISSN	0022-1295
DOI	10.1085/jgp.201611599
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Article ; Online: Ligand sensitivity of type-1 inositol 1,4,5-trisphosphate receptor is enhanced by the D2594K mutation.

Tambeaux, Allison / Aguilar-Sánchez, Yuriana / Santiago, Demetrio J / Mascitti, Madeleine / DiNovo, Karyn M / Mejía-Alvarez, Rafael / Fill, Michael / Wayne Chen, S R / Ramos-Franco, Josefina

Pflugers Archiv : European journal of physiology

2023 Volume 475, Issue 5, Page(s) 569–581

Abstract: Inositol 1,4,5-trisphosphate receptor ( ... ...

Abstract	Inositol 1,4,5-trisphosphate receptor (IP
MeSH term(s)	Inositol 1,4,5-Trisphosphate Receptors/genetics ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Ligands ; Calcium Signaling ; Mutation ; Endoplasmic Reticulum/metabolism ; Calcium/metabolism
Chemical Substances	Inositol 1,4,5-Trisphosphate Receptors ; Ligands ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2023-03-07
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-023-02796-x
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Article ; Online: Intact Heart Loose Patch Photolysis Reveals Ionic Current Kinetics During Ventricular Action Potentials.

Ramos-Franco, Josefina / Aguilar-Sanchez, Yuriana / Escobar, Ariel L

Circulation research

2016 Volume 118, Issue 2, Page(s) 203–215

Abstract: Rationale: Assessing the underlying ionic currents during a triggered action potential (AP) in intact perfused hearts offers the opportunity to link molecular mechanisms with pathophysiological problems in cardiovascular research. The developed loose ... ...

Abstract	Rationale: Assessing the underlying ionic currents during a triggered action potential (AP) in intact perfused hearts offers the opportunity to link molecular mechanisms with pathophysiological problems in cardiovascular research. The developed loose patch photolysis technique can provide striking new insights into cardiac function at the whole heart level during health and disease. Objective: To measure transmembrane ionic currents during an AP to determine how and when surface Ca(2+) influx that triggers Ca(2+)-induced Ca(2+) release occurs and how Ca(2+)-activated conductances can contribute to the genesis of AP phase 2. Methods and results: Loose patch photolysis allows the measurement of transmembrane ionic currents in intact hearts. During a triggered AP, a voltage-dependent Ca(2+) conductance was fractionally activated (dis-inhibited) by rapidly photo-degrading nifedipine, the Ca(2+) channel blocker. The ionic currents during a mouse ventricular AP showed a fast early component and a slower late component. Pharmacological studies established that the molecular basis underlying the early component was driven by an influx of Ca(2+) through the L-type channel, CaV 1.2. The late component was identified as an Na(+)-Ca(2+) exchanger current mediated by Ca(2+) released from the sarcoplasmic reticulum. Conclusions: The novel loose patch photolysis technique allowed the dissection of transmembrane ionic currents in the intact heart. We were able to determine that during an AP, L-type Ca(2+) current contributes to phase 1, whereas Na(+)-Ca(2+) exchanger contributes to phase 2. In addition, loose patch photolysis revealed that the influx of Ca(2+) through L-type Ca(2+) channels terminates because of voltage-dependent deactivation and not by Ca(2+)-dependent inactivation, as commonly believed.
MeSH term(s)	Action Potentials/drug effects ; Animals ; Calcium Channel Blockers/chemistry ; Calcium Channel Blockers/pharmacology ; Calcium Channels, L-Type/drug effects ; Calcium Channels, L-Type/metabolism ; Calcium Signaling/drug effects ; Excitation Contraction Coupling ; Heart Ventricles/drug effects ; Heart Ventricles/metabolism ; Isolated Heart Preparation ; Kinetics ; Male ; Mice, Inbred BALB C ; Microscopy, Fluorescence/methods ; Nifedipine/chemistry ; Nifedipine/pharmacology ; Patch-Clamp Techniques ; Photolysis ; Sarcoplasmic Reticulum/metabolism ; Sodium-Calcium Exchanger/metabolism
Chemical Substances	CACNA1C protein, mouse ; Calcium Channel Blockers ; Calcium Channels, L-Type ; Sodium-Calcium Exchanger ; Nifedipine (I9ZF7L6G2L)
Language	English
Publishing date	2016-01-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.115.307399
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Article ; Online: A gain-of-function mutation in the ITPR1 gating domain causes male infertility in mice.

Sun, Bo / Ni, Mingke / Tian, Shanshan / Guo, Wenting / Cai, Shitian / Sondergaard, Mads T / Chen, Yongxiang / Mu, Yongxin / Estillore, John P / Wang, Ruiwu / Chen, Ju / Overgaard, Michael T / Fill, Michael / Ramos-Franco, Josefina / Nyegaard, Mette / Wayne Chen, Sui Rong

Journal of cellular physiology

2022 Volume 237, Issue 8, Page(s) 3305–3316

Abstract: Inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is an intracellular ... ...

Abstract	Inositol 1,4,5-trisphosphate receptor 1 (ITPR1) is an intracellular Ca
MeSH term(s)	Animals ; Calcium/metabolism ; Gain of Function Mutation ; HEK293 Cells ; Humans ; Infertility, Male/genetics ; Inositol 1,4,5-Trisphosphate ; Inositol 1,4,5-Trisphosphate Receptors/genetics ; Male ; Mice ; Mutation/genetics
Chemical Substances	ITPR1 protein, human ; Inositol 1,4,5-Trisphosphate Receptors ; Itpr1 protein, mouse ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.30783
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Article: Transmural Autonomic Regulation of Cardiac Contractility at the Intact Heart Level.

Aguilar-Sanchez, Yuriana / Rodriguez de Yurre, Ainhoa / Argenziano, Mariana / Escobar, Ariel L / Ramos-Franco, Josefina

Frontiers in physiology

2019 Volume 10, Page(s) 773

Abstract: The relationship between cardiac excitability and contractility depends on when ... ...

Abstract	The relationship between cardiac excitability and contractility depends on when Ca
Language	English
Publishing date	2019-07-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2019.00773
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Article: A Type 2 Ryanodine Receptor Variant in the Helical Domain 2 Associated with an Impairment of the Adrenergic Response.

Blancard, Malorie / Touat-Hamici, Zahia / Aguilar-Sanchez, Yuriana / Yin, Liheng / Vaksmann, Guy / Roux-Buisson, Nathalie / Fressart, Véronique / Denjoy, Isabelle / Klug, Didier / Neyroud, Nathalie / Ramos-Franco, Josefina / Gomez, Ana Maria / Guicheney, Pascale

Journal of personalized medicine

2021 Volume 11, Issue 6

Abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is triggered by exercise or acute emotion in patients with normal resting electrocardiogram. The major disease-causing gene ... ...

Abstract	Catecholaminergic polymorphic ventricular tachycardia (CPVT) is triggered by exercise or acute emotion in patients with normal resting electrocardiogram. The major disease-causing gene is
Language	English
Publishing date	2021-06-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm11060579
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Article ; Online: Ryanodol action on calcium sparks in ventricular myocytes.

Ramos-Franco, Josefina / Gomez, Ana M / Nani, Alma / Liu, Yiwei / Copello, Julio A / Fill, Michael

Pflugers Archiv : European journal of physiology

2010 Volume 460, Issue 4, Page(s) 767–776

Abstract: The action of ryanodol on single cardiac ryanodine receptor (RyR2) channels in bilayers and local RyR2-mediated Ca(2+) release events (Ca(2+) sparks) in ventricular myocytes was defined. At the single-channel level, ryanodol intermittently modified ... ...

Abstract	The action of ryanodol on single cardiac ryanodine receptor (RyR2) channels in bilayers and local RyR2-mediated Ca(2+) release events (Ca(2+) sparks) in ventricular myocytes was defined. At the single-channel level, ryanodol intermittently modified single channels into a long-lived subconductance state with an average duration of 3.8 +/- 0.2 s. Unlike ryanodine, ryanodol did not change the open probability (Po) of unmodified channels, and high concentrations did not promote full-channel closure. Ryanodol action was Po dependent with the K (D) varying roughly from 20 to 80 muM as Po changed from approximately 0.2 to 1, respectively. Ryanodol preferentially bound during long channel openings. In intact and permeabilized rat myocytes, ryanodol evoked trains of sparks at active release sites resulting in a significant increase in overall spark frequency. Ryanodol did not increase the number of active release sites. Long-lived Ca(2+) release events were observed but infrequently, and ryanodol action was readily reversed upon drug washout. We propose that ryanodol modifies a few channels during a Ca(2+) spark. These modified channels mediate a sustained low-intensity Ca(2+) release that repeatedly triggers sparks at the same release site. We conclude that ryanodol is an easily generated reversible probe that can be effectively used to explore RyR2-mediated Ca(2+) release in cells.
MeSH term(s)	Animals ; Calcium Signaling/drug effects ; Calcium Signaling/physiology ; Diterpenes/chemical synthesis ; Diterpenes/pharmacology ; Heart Ventricles/drug effects ; Heart Ventricles/metabolism ; Male ; Microscopy, Confocal ; Muscle Cells/drug effects ; Muscle Cells/metabolism ; Rats ; Rats, Wistar ; Ryanodine Receptor Calcium Release Channel/drug effects ; Ryanodine Receptor Calcium Release Channel/metabolism ; Sarcoplasmic Reticulum/drug effects ; Sarcoplasmic Reticulum/metabolism
Chemical Substances	Diterpenes ; Ryanodine Receptor Calcium Release Channel ; ryanodanol
Language	English
Publishing date	2010-04-24
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-010-0839-8
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Article ; Online: Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation.

Yin, Liheng / Zahradnikova, Alexandra / Rizzetto, Riccardo / Boncompagni, Simona / Rabesahala de Meritens, Camille / Zhang, Yadan / Joanne, Pierre / Marqués-Sulé, Elena / Aguilar-Sánchez, Yuriana / Fernández-Tenorio, Miguel / Villejoubert, Olivier / Li, Linwei / Wang, Yue Yi / Mateo, Philippe / Nicolas, Valérie / Gerbaud, Pascale / Lai, F Anthony / Perrier, Romain / Álvarez, Julio L /

Niggli, Ernst / Valdivia, Héctor H / Valdivia, Carmen R / Ramos-Franco, Josefina / Zorio, Esther / Zissimopoulos, Spyros / Protasi, Feliciano / Benitah, Jean-Pierre / Gómez, Ana M

Circulation research

2021 Volume 129, Issue 3, Page(s) e35–e52

Abstract: Figure: see text]. ...

Abstract	[Figure: see text].
MeSH term(s)	Action Potentials ; Animals ; Binding Sites ; Calcium Signaling ; Cells, Cultured ; HEK293 Cells ; Humans ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mutation ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/physiology ; Myocytes, Cardiac/ultrastructure ; Protein Binding ; Ryanodine Receptor Calcium Release Channel/chemistry ; Ryanodine Receptor Calcium Release Channel/genetics ; Ryanodine Receptor Calcium Release Channel/metabolism ; Tachycardia, Ventricular/genetics ; Tachycardia, Ventricular/metabolism ; Tachycardia, Ventricular/pathology
Chemical Substances	Membrane Proteins ; RyR2 protein, human ; Ryanodine Receptor Calcium Release Channel ; junctophilin
Language	English
Publishing date	2021-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.121.319094
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Article ; Online: Role of inositol 1,4,5-trisphosphate in the regulation of ventricular Ca(2+) signaling in intact mouse heart.

Escobar, Ariel L / Perez, Claudia G / Reyes, Mariano E / Lucero, Sarah G / Kornyeyev, Dmytro / Mejía-Alvarez, Rafael / Ramos-Franco, Josefina

Journal of molecular and cellular cardiology

2012 Volume 53, Issue 6, Page(s) 768–779

Abstract: Inositol 1,4,5-trisphosphate (InsP(3)R)-mediated Ca(2+) signaling is a major pathway regulating multiple cellular functions in excitable and non-excitable cells. Although InsP(3)-mediated Ca(2+) signaling has been extensively described, its influence on ... ...

Abstract	Inositol 1,4,5-trisphosphate (InsP(3)R)-mediated Ca(2+) signaling is a major pathway regulating multiple cellular functions in excitable and non-excitable cells. Although InsP(3)-mediated Ca(2+) signaling has been extensively described, its influence on ventricular myocardium activity has not been addressed in contracting hearts at the whole-organ level. In this work, InsP(3)-sensitive intracellular Ca(2+) signals were studied in intact hearts using laser scanning confocal microscopy and pulsed local-field fluorescence microscopy. Intracellular [InsP(3)] was rapidly increased by UV flash photolysis of membrane-permeant caged InsP(3). Our results indicate that the basal [Ca(2+)] increased after the flash photolysis of caged InsP(3) without affecting the action potential (AP)-induced Ca(2+) transients. The amplitude of the basal [Ca(2+)] elevation depended on the intracellular [InsP(3)] reached after the UV flash. Pretreatment with ryanodine failed to abolish the InsP(3)-induced Ca(2+) release (IICR), indicating that this response was not mediated by ryanodine receptors (RyR). Thapsigargin prevented Ca(2+) release from both RyR- and InsP(3)R-containing Ca(2+) stores, suggesting that these pools have similar Ca(2+) reuptake mechanisms. These results were reproduced in acutely isolated cells where photorelease of InsP(3) was able to induce changes in endothelial cells but not in AP-induced transients from cardiomyocytes. Taken together, these results suggest that IICR does not directly regulate cardiac excitation-contraction coupling. To our knowledge, this is the first demonstration of IICR in intact hearts. Consequently, our work provides a reference framework of the spatiotemporal attributes of the IICR under physiological conditions.
MeSH term(s)	Action Potentials/drug effects ; Animals ; Calcium/metabolism ; Calcium Signaling/drug effects ; Dose-Response Relationship, Drug ; Heart/drug effects ; Heart/physiology ; Heart Ventricles/drug effects ; Heart Ventricles/metabolism ; In Vitro Techniques ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol 1,4,5-Trisphosphate/pharmacology ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Kinetics ; Mice ; Myocytes, Cardiac/metabolism ; Protein Binding ; Ryanodine Receptor Calcium Release Channel/metabolism
Chemical Substances	Inositol 1,4,5-Trisphosphate Receptors ; Ryanodine Receptor Calcium Release Channel ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2012-08-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2012.08.019
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