2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes
Context: 2,3-Butanedione monoxime (BDM), an uncoupler of cardiac contraction, is commonly used in enzymatic dissociations to prevent hypercontraction of cardiomyocytes and in cardioplegic solutions to decrease oxygen demand during surgery. However, BDM affects multiple cellular systems including the...
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| Format: | Article |
| Language: | English |
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GarVal Editorial Ltda.
2016-12-01
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| Series: | Journal of Pharmacy & Pharmacognosy Research |
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| Online Access: | http://jppres.com/jppres/pdf/vol4/jppres16.150_4.6.206.pdf |
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| author | Julio Alvarez-Collazo Ana Iris López-Medina Loipa Galán-Martínez Julio L. Alvarez |
| author_facet | Julio Alvarez-Collazo Ana Iris López-Medina Loipa Galán-Martínez Julio L. Alvarez |
| author_sort | Julio Alvarez-Collazo |
| collection | DOAJ |
| description | Context: 2,3-Butanedione monoxime (BDM), an uncoupler of cardiac contraction, is commonly used in enzymatic dissociations to prevent hypercontraction of cardiomyocytes and in cardioplegic solutions to decrease oxygen demand during surgery. However, BDM affects multiple cellular systems including the L-type Ca2+ current (ICaL). If its phosphatase activity is the mechanism underlying the decrease ICaL in cardiomyocytes is a still unresolved question.
Aims: To study the effects of BDM on ICaL of rat ventricular cardiomyocytes focusing our attention on the response of ICaL to β-adrenergic stimulation.
Methods: The whole-cell patch-clamp method was used to study ICaL in enzymatically dissociated rat ventricular cardiomyocytes.
Results: Extracellular BDM (5 mM) decreased peak ICaL by ≈45%, slowed its fast inactivation but accelerated its slow inactivation. Cardiomyocytes incubated in BDM (≥ 30 min; 5 mM) perfused with normal extracellular solution, showed normal ICaL properties. However, extracellular BDM (in cardiomyocytes incubated in BDM or not) markedly reduced the response of ICaL to isoproterenol (1 µM). BDM also strongly attenuated the increase of ICaL in cardiomyocytes intracellularly perfused with cyclic AMP (50 µM).
Conclusions: The decrease of basal ICaL by BDM is not related to its dephosphorylation action. Its effect on the Ca2+ channel occurs most probably in a site in the extracellular side or within the sarcolemmal membrane. Due to its phosphatase action, BDM strongly attenuates the response of ICaL to β-adrenergic stimulation. These actions of BDM must be taken into account both for its use in the dissociation of cardiomyocytes and in cardioplegic solutions and myocardial preservation. |
| first_indexed | 2024-12-13T20:17:53Z |
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| id | doaj.art-64a9dc0fd4a1449da0879d9fb5997ff5 |
| institution | Directory Open Access Journal |
| issn | 0719-4250 |
| language | English |
| last_indexed | 2024-12-13T20:17:53Z |
| publishDate | 2016-12-01 |
| publisher | GarVal Editorial Ltda. |
| record_format | Article |
| series | Journal of Pharmacy & Pharmacognosy Research |
| spelling | doaj.art-64a9dc0fd4a1449da0879d9fb5997ff52022-12-21T23:32:45ZengGarVal Editorial Ltda.Journal of Pharmacy & Pharmacognosy Research0719-42502016-12-01462062162,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytesJulio Alvarez-Collazo0Ana Iris López-Medina1Loipa Galán-Martínez2Julio L. Alvarez3Laboratorio de Electrofisiología. Instituto de Cardiología y Cirugía Cardiovascular. Paseo y 17, Vedado, CP 10400, La Habana. Cuba. Laboratory of Ion Channel Research and TRP Research Platform Leuven, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratorio de Electrofisiología. Instituto de Cardiología y Cirugía Cardiovascular. Paseo y 17, Vedado, CP 10400, La Habana. CubaLaboratorio de Electrofisiología. Instituto de Cardiología y Cirugía Cardiovascular. Paseo y 17, Vedado, CP 10400, La Habana. CubaLaboratorio de Electrofisiología. Instituto de Cardiología y Cirugía Cardiovascular. Paseo y 17, Vedado, CP 10400, La Habana. CubaContext: 2,3-Butanedione monoxime (BDM), an uncoupler of cardiac contraction, is commonly used in enzymatic dissociations to prevent hypercontraction of cardiomyocytes and in cardioplegic solutions to decrease oxygen demand during surgery. However, BDM affects multiple cellular systems including the L-type Ca2+ current (ICaL). If its phosphatase activity is the mechanism underlying the decrease ICaL in cardiomyocytes is a still unresolved question. Aims: To study the effects of BDM on ICaL of rat ventricular cardiomyocytes focusing our attention on the response of ICaL to β-adrenergic stimulation. Methods: The whole-cell patch-clamp method was used to study ICaL in enzymatically dissociated rat ventricular cardiomyocytes. Results: Extracellular BDM (5 mM) decreased peak ICaL by ≈45%, slowed its fast inactivation but accelerated its slow inactivation. Cardiomyocytes incubated in BDM (≥ 30 min; 5 mM) perfused with normal extracellular solution, showed normal ICaL properties. However, extracellular BDM (in cardiomyocytes incubated in BDM or not) markedly reduced the response of ICaL to isoproterenol (1 µM). BDM also strongly attenuated the increase of ICaL in cardiomyocytes intracellularly perfused with cyclic AMP (50 µM). Conclusions: The decrease of basal ICaL by BDM is not related to its dephosphorylation action. Its effect on the Ca2+ channel occurs most probably in a site in the extracellular side or within the sarcolemmal membrane. Due to its phosphatase action, BDM strongly attenuates the response of ICaL to β-adrenergic stimulation. These actions of BDM must be taken into account both for its use in the dissociation of cardiomyocytes and in cardioplegic solutions and myocardial preservation.http://jppres.com/jppres/pdf/vol4/jppres16.150_4.6.206.pdf2-3-butanedione monoximecalcium channelscardiomyocytes; myocardial preservation; patch-clampcardiomyocytesmyocardial preservationpatch-clamp |
| spellingShingle | Julio Alvarez-Collazo Ana Iris López-Medina Loipa Galán-Martínez Julio L. Alvarez 2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes Journal of Pharmacy & Pharmacognosy Research 2-3-butanedione monoxime calcium channels cardiomyocytes; myocardial preservation; patch-clamp cardiomyocytes myocardial preservation patch-clamp |
| title | 2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes |
| title_full | 2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes |
| title_fullStr | 2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes |
| title_full_unstemmed | 2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes |
| title_short | 2,3-Butanedione monoxime attenuates the β-adrenergic response of the L-type Ca2+ current in rat ventricular cardiomyocytes |
| title_sort | 2 3 butanedione monoxime attenuates the β adrenergic response of the l type ca2 current in rat ventricular cardiomyocytes |
| topic | 2-3-butanedione monoxime calcium channels cardiomyocytes; myocardial preservation; patch-clamp cardiomyocytes myocardial preservation patch-clamp |
| url | http://jppres.com/jppres/pdf/vol4/jppres16.150_4.6.206.pdf |
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