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Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level
BACKGROUND: Abnormal Ca(2+) transients are often observed in heart muscles under a variety of pathophysiological conditions including ventricular tachycardia. To clarify whether these abnormal Ca(2+) transients can be attributed to abnormal action potential generation or abnormal Ca(2+) handling/exc...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740872/ https://www.ncbi.nlm.nih.gov/pubmed/19768114 http://dx.doi.org/10.1371/journal.pone.0007069 |
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author | Nishizawa, Hiroto Suzuki, Takeshi Shioya, Takao Nakazato, Yuji Daida, Hiroyuki Kurebayashi, Nagomi |
author_facet | Nishizawa, Hiroto Suzuki, Takeshi Shioya, Takao Nakazato, Yuji Daida, Hiroyuki Kurebayashi, Nagomi |
author_sort | Nishizawa, Hiroto |
collection | PubMed |
description | BACKGROUND: Abnormal Ca(2+) transients are often observed in heart muscles under a variety of pathophysiological conditions including ventricular tachycardia. To clarify whether these abnormal Ca(2+) transients can be attributed to abnormal action potential generation or abnormal Ca(2+) handling/excitation-contraction (EC) coupling, we developed a procedure to determine Ca(2+) and action potential signals at the cellular level in isolated heart tissues. METHODOLOGY/PRINCIPAL FINDINGS: After loading ventricular papillary muscle with rhod-2 and di-4-ANEPPS, mono-wavelength fluorescence images from rhod-2 and ratiometric images of two wavelengths of emission from di-4-ANEPPS were sequentially obtained. To mimic the ventricular tachycardia, the ventricular muscles were field-stimulated in non-flowing Krebs solution which elicited abnormal Ca(2+) transients. For the failed and alternating Ca(2+) transient generation, there were two types of causes, i.e., failed or abnormal action potential generation and abnormal EC coupling. In cells showing delayed initiation of Ca(2+) transients with field stimulation, action potential onset was delayed and the rate of rise was slower than in healthy cells. Similar delayed onset was also observed in the presence of heptanol, an inhibitor of gap junction channels but having a non-specific channel blocking effect. A Na(+) channel blocker, on the other hand, reduced the rate of rise of the action potentials but did not result in desynchronization of the action potentials. The delayed onset of action potentials can be explained primarily by impaired gap junctions and partly by Na(+) channel inactivation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that there are multiple patterns for the causes of abnormal Ca(2+) signals and that our methods are useful for investigating the physiology and pathophysiology of heart muscle. |
format | Text |
id | pubmed-2740872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27408722009-09-21 Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level Nishizawa, Hiroto Suzuki, Takeshi Shioya, Takao Nakazato, Yuji Daida, Hiroyuki Kurebayashi, Nagomi PLoS One Research Article BACKGROUND: Abnormal Ca(2+) transients are often observed in heart muscles under a variety of pathophysiological conditions including ventricular tachycardia. To clarify whether these abnormal Ca(2+) transients can be attributed to abnormal action potential generation or abnormal Ca(2+) handling/excitation-contraction (EC) coupling, we developed a procedure to determine Ca(2+) and action potential signals at the cellular level in isolated heart tissues. METHODOLOGY/PRINCIPAL FINDINGS: After loading ventricular papillary muscle with rhod-2 and di-4-ANEPPS, mono-wavelength fluorescence images from rhod-2 and ratiometric images of two wavelengths of emission from di-4-ANEPPS were sequentially obtained. To mimic the ventricular tachycardia, the ventricular muscles were field-stimulated in non-flowing Krebs solution which elicited abnormal Ca(2+) transients. For the failed and alternating Ca(2+) transient generation, there were two types of causes, i.e., failed or abnormal action potential generation and abnormal EC coupling. In cells showing delayed initiation of Ca(2+) transients with field stimulation, action potential onset was delayed and the rate of rise was slower than in healthy cells. Similar delayed onset was also observed in the presence of heptanol, an inhibitor of gap junction channels but having a non-specific channel blocking effect. A Na(+) channel blocker, on the other hand, reduced the rate of rise of the action potentials but did not result in desynchronization of the action potentials. The delayed onset of action potentials can be explained primarily by impaired gap junctions and partly by Na(+) channel inactivation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that there are multiple patterns for the causes of abnormal Ca(2+) signals and that our methods are useful for investigating the physiology and pathophysiology of heart muscle. Public Library of Science 2009-09-21 /pmc/articles/PMC2740872/ /pubmed/19768114 http://dx.doi.org/10.1371/journal.pone.0007069 Text en Nishizawa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nishizawa, Hiroto Suzuki, Takeshi Shioya, Takao Nakazato, Yuji Daida, Hiroyuki Kurebayashi, Nagomi Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level |
title | Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level |
title_full | Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level |
title_fullStr | Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level |
title_full_unstemmed | Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level |
title_short | Causes of Abnormal Ca(2+) Transients in Guinea Pig Pathophysiological Ventricular Muscle Revealed by Ca(2+) and Action Potential Imaging at Cellular Level |
title_sort | causes of abnormal ca(2+) transients in guinea pig pathophysiological ventricular muscle revealed by ca(2+) and action potential imaging at cellular level |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740872/ https://www.ncbi.nlm.nih.gov/pubmed/19768114 http://dx.doi.org/10.1371/journal.pone.0007069 |
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