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Article ; Online: Cardiac effects and toxicity of chloroquine: a short update.

Mubagwa, Kanigula

International journal of antimicrobial agents

2020 Volume 56, Issue 2, Page(s) 106057

Abstract: There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of ... ...

Abstract	There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na
MeSH term(s)	Betacoronavirus ; COVID-19 ; Chloroquine/adverse effects ; Chloroquine/therapeutic use ; Coronavirus Infections/drug therapy ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; SARS-CoV-2
Chemical Substances	Chloroquine (886U3H6UFF)
Keywords	covid19
Language	English
Publishing date	2020-06-19
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2020.106057
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Article: Chloroquine cardiac effects and toxicityA short update

Mubagwa, K.

International Journal of Antimicrobial Agents

Abstract: There is currently an increased interest in using the antimalarials chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as COVID-19 However, risks of cardiotoxic effects tend to limit their ... ...

Abstract	There is currently an increased interest in using the antimalarials chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as COVID-19 However, risks of cardiotoxic effects tend to limit their use The effects of these drugs on the electrical and mechanical activities of the heart, as well as on the remodeling of the cardiac tissue are presented, and the underlying molecular and cellular mechanisms discussed The drugs can have proarrhythmic as well as antiarrhythmic actions, resulting from their inhibition of ion channels, including voltage-dependent Nasup+/sup and Casup2+/sup channels, background and voltage-dependent Ksup+/sup channels, and pacemaker channels The drugs also exert a vagolytic effect, due at least in part to a muscarinic receptor antagonist action They also interfere with the normal autophagy flux, an effect which could aggravate ischemia/reperfusion injury or post-infarct remodeling Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #828986
Database	COVID19

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Article: Cardiac effects and toxicity of chloroquine: a short update

Mubagwa, Kanigula

Int J Antimicrob Agents

Abstract: ... including voltage-dependent Na+ and Ca2+ channels, background and voltage-dependent K+ channels, and ...

Abstract	There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na+ and Ca2+ channels, background and voltage-dependent K+ channels, and pacemaker channels. The drugs also exert a vagolytic effect due at least in part to a muscarinic receptor antagonist action. They also interfere with normal autophagy flux, an effect that could aggravate ischaemia/reperfusion injury or post-infarct remodelling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #611607
Database	COVID19

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Article: Cardiac effects and toxicity of chloroquine: a short update

Mubagwa, Kanigula

International journal of antimicrobial agents. 2020 Aug., v. 56, no. 2

2020

Abstract: ... including voltage-dependent Na⁺ and Ca²⁺ channels, background and voltage-dependent K⁺ channels, and ...

Abstract	There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na⁺ and Ca²⁺ channels, background and voltage-dependent K⁺ channels, and pacemaker channels. The drugs also exert a vagolytic effect due at least in part to a muscarinic receptor antagonist action. They also interfere with normal autophagy flux, an effect that could aggravate ischaemia/reperfusion injury or post-infarct remodelling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.
Keywords	Coronavirus infections ; Orthocoronavirinae ; antagonists ; autophagy ; calcium ; chloroquine ; heart ; ion channels ; ischemia ; muscarine receptors ; reperfusion injury ; risk ; toxicity
Language	English
Dates of publication	2020-08
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-light
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2020.106057
Database	NAL-Catalogue (AGRICOLA)

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Article: Emerging role of transient receptor potential (TRP) ion channels in cardiac fibroblast pathophysiology.

Gwanyanya, Asfree / Mubagwa, Kanigula

Frontiers in physiology

2022 Volume 13, Page(s) 968393

Abstract: Cardiac fibroblasts make up a major proportion of non-excitable cells in the heart and contribute to the cardiac structural integrity and maintenance of the extracellular matrix. During myocardial injury, fibroblasts can be activated to trans- ... ...

Abstract	Cardiac fibroblasts make up a major proportion of non-excitable cells in the heart and contribute to the cardiac structural integrity and maintenance of the extracellular matrix. During myocardial injury, fibroblasts can be activated to trans-differentiate into myofibroblasts, which secrete extracellular matrix components as part of healing, but may also induce cardiac fibrosis and pathological cardiac structural and electrical remodeling. The mechanisms regulating such cellular processes still require clarification, but the identification of transient receptor potential (TRP) channels in cardiac fibroblasts could provide further insights into the fibroblast-related pathophysiology. TRP proteins belong to a diverse superfamily, with subgroups such as the canonical (TRPC), vanilloid (TRPV), melastatin (TRPM), ankyrin (TRPA), polycystin (TRPP), and mucolipin (TRPML). Several TRP proteins form non-selective channels that are permeable to cations like Na
Language	English
Publishing date	2022-10-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.968393
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Article: Deterioration of the protein kinase C-K(ATP) channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits.

Pongo, E / Balla, Z / Mubagwa, K / Flameng, W / Edes, I / Szilvassy, Z / Ferdinandy, P

European journal of pharmacology

2001 Volume 418, Issue 3, Page(s) 217–223

Abstract: ... flow and cardiac function, induced by protein kinase C and ATP-sensitive K(+) (K(ATP)) channel ... an index of ventricular contractility. Glyburide (5-50 microM), a K(ATP) channel inhibitor, blocked ... a K(ATP) channel activator. Neither the protein kinase C modulators nor glyburide produced any effect ...

Abstract	We studied the effect of experimental hypercholesterolaemia/atherosclerosis on changes in coronary flow and cardiac function, induced by protein kinase C and ATP-sensitive K(+) (K(ATP)) channel modulators in isolated Langendorff-perfused rabbit hearts. Both phorbol 12-myristate-13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB, 0.1 microM each), activators of protein kinase C, decreased, whereas staurosporine, (0.1 microM), a protein kinase C inhibitor, increased coronary flow and left ventricular dP/dt, an index of ventricular contractility. Glyburide (5-50 microM), a K(ATP) channel inhibitor, blocked the effect of staurosporine. The phorbol esters were without effect in the presence of pinacidil (5 microM), a K(ATP) channel activator. Neither the protein kinase C modulators nor glyburide produced any effect on coronary flow and left ventricular contractility, when the hearts were prepared from animals either maintained on a cholesterol (1.5%)-enriched diet or treated with lovastatin (5 mg/kg/day per os). Treatment with farnesol (1 mg/kg twice a day for 7 days intravenously) restored the reactivity of hearts from either hypercholesterolaemic or lovastatin-treated animals to protein kinase C modulators. We conclude that non-cholesterol mevalonate products are necessary for the functional integrity of the protein kinase C-K(ATP) channel pathway in the rabbit heart.
MeSH term(s)	Adenosine Triphosphate/physiology ; Animals ; Coronary Circulation/drug effects ; Coronary Circulation/physiology ; Enzyme Inhibitors/pharmacology ; Heart Ventricles/drug effects ; Heart Ventricles/physiopathology ; Hypercholesterolemia/physiopathology ; In Vitro Techniques ; Male ; Phorbol 12,13-Dibutyrate/pharmacology ; Potassium Channels/physiology ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/metabolism ; Rabbits ; Staurosporine/pharmacology ; Tetradecanoylphorbol Acetate/pharmacology
Chemical Substances	Enzyme Inhibitors ; Potassium Channels ; Phorbol 12,13-Dibutyrate (37558-16-0) ; Adenosine Triphosphate (8L70Q75FXE) ; Protein Kinase C (EC 2.7.11.13) ; Staurosporine (H88EPA0A3N) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	2001-04-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/s0014-2999(01)00954-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Differential time course for desensitization to muscarinic effects on K+ and Ca2+ channels.

Mubagwa, K / Gilbert, J C / Pappano, A J

Pflugers Archiv : European journal of physiology

1994 Volume 428, Issue 5-6, Page(s) 542–551

Abstract: The time course of muscarinic effects on K and Ca currents was investigated at 22-24 degrees C ... short exposures to 100 microM acetylcholine (ACh) or carbachol (CCh) reproducibly induced outward K ... control of K and Ca channels. ...

Abstract	The time course of muscarinic effects on K and Ca currents was investigated at 22-24 degrees C in guinea-pig atrial myocytes, using the whole-cell voltage clamp. At a holding potential of -40 or -50 mV, short exposures to 100 microM acetylcholine (ACh) or carbachol (CCh) reproducibly induced outward K currents (IK,ACh). During long exposures to these agonists, IK,ACh faded with time. In cells not dialysed with guanosine triphosphate (GTP), IK,ACh could dissipate completely following 15-20 min of agonist exposure. After agonist washout, lost sensitivity was not recovered. In cells dialysed with GTP (0.2-1 mM), IK,ACh still faded but normal sensitivity to agonists was restored with washout. Fade of IK,ACh was not prevented by intracellular heparin or dextran, excluding the involvement of either beta-adrenergic or muscarinic receptor kinase. IK,ACh induced by bethanechol or adenosine also faded, and subsequent CCh application after washout revealed a diminished response. Intracellular guanosine-5'-o-(3-thiotriphosphate (GTP gamma S) induced IK,ACh which faded, and subsequent exposure to CCh was without effect. Equally, after full desensitization with CCh, GTP gamma S failed to induce IK,ACh. The Ca current (ICa) was activated by voltage steps to 0 mV and increased with 1-3 microM isoproterenol. This increase could be reversed by CCh, even when IK,ACh had completely faded. Prolonged muscarinic agonist exposure sometimes also caused fade of the effect on ICa, which always occurred after loss of IK,ACh. The results show that desensitization is heterologous and may involve the guanine nucleotide-binding (G) protein. The differential desensitization to the effects on IK,ACh and ICa suggests the involvement of two different signalling pathways in the muscarinic control of K and Ca channels.
MeSH term(s)	Acetylcholine/pharmacology ; Animals ; Calcium Channels/physiology ; Carbachol/pharmacology ; Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology ; Guanosine Triphosphate/pharmacology ; Guinea Pigs ; Muscarine/metabolism ; Parasympathetic Nervous System/physiology ; Potassium Channels/physiology
Chemical Substances	Calcium Channels ; Potassium Channels ; Guanosine 5'-O-(3-Thiotriphosphate) (37589-80-3) ; Muscarine (7T101UWZ5W) ; Guanosine Triphosphate (86-01-1) ; Carbachol (8Y164V895Y) ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	1994-10
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/bf00374576
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Signalling between G-protein-coupled receptors and TASK1 channels.

Mubagwa, Kanigula

Cardiovascular research

2012 Volume 97, Issue 1, Page(s) 10–12

MeSH term(s)	Animals ; Endothelin-1/pharmacology ; Ion Channel Gating ; Myocytes, Cardiac/enzymology ; Potassium Channel Blockers/pharmacology ; Potassium Channels, Tandem Pore Domain/antagonists & inhibitors ; Type C Phospholipases/metabolism
Chemical Substances	Endothelin-1 ; Potassium Channel Blockers ; Potassium Channels, Tandem Pore Domain ; potassium channel subfamily K member 3 (1HQ3YCN4GS) ; Type C Phospholipases (EC 3.1.4.-)
Language	English
Publishing date	2012-11-19
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvs343
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Article ; Online: Detection of TRPM6 and TRPM7 Proteins in Normal and Diseased Cardiac Atrial Tissue and Isolated Cardiomyocytes.

Andriulė, Inga / Pangonytė, Dalia / Gwanyanya, Asfree / Karčiauskas, Dainius / Mubagwa, Kanigula / Mačianskienė, Regina

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal ...

Abstract	Magnesium-sensitive transient receptor potential melastatin (TRPM) ion channels, TRPM6 and TRPM7, are present in several organs, but their roles in the heart remain unclear. Therefore, here, we studied the expression patterns of TRPM6 and TRPM7 in normal and diseased myocardium. Cardiac atrial tissue and cardiomyocytes were obtained from healthy pigs and undiseased human hearts as well as from hearts of patients with ischemic heart disease (IHD) or atrial fibrillation (AF). Immunofluorescence and ELISA were used to detect TRP proteins. TRPM6 and TRPM7 immunofluorescence signals, localized at/near the cell surface or intracellularly, were detected in pig and human atrial tissues. The TRP channel modulators carvacrol (CAR, 100 µM) or 2-aminoethoxydiphenyl borate (2-APB, 500 µM) decreased the TRPM7 signal, but enhanced that of TRPM6. At a higher concentration (2 mM), 2-APB enhanced the signals of both proteins. TRPM6 and TRPM7 immunofluorescence signals and protein concentrations were increased in atrial cells and tissues from IHD or AF patients. TRPM6 and TRPM7 proteins were both detected in cardiac atrial tissue, with relatively similar subcellular localization, but distinctive drug sensitivity profiles. Their upregulated expression in IHD and AF suggests a possible role of the channels in cardiac atrial disease.
Language	English
Publishing date	2022-11-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232314860
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book: ACETYLCHOLINE AND THE ELECTROPHYSIOLOGICAL PROPERTIES OF RABBIT CARDIAC PURKINJE FIBRES

MUBAGWA, KANIGULA

1984

Size	175 S.
Document type	Book
Note	LEUVEN, UNIV., DISS., 1984
HBZ-ID	HT002734427
Database	Catalogue ZB MED Medicine, Health

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85 E 1243	order for loan	Magazin

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