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Loay Lubbad - One of the best experts on this subject based on the ideXlab platform.
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Propagation characteristics of the Electrical Impulse in the normal and obstructed ureter as determined at high electrophysiological resolution: Electrical ImpulseS PROPAGATION IN URETERIC OBSTRUCTION
BJU International, 2011Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:What’s known on the subject? and What does the study add? Ureteric obstruction resulted in a differential change in the Electrical activity in the proximal and distal ureter with the proximal ureter having an immediate increase in the frequency of Electrical Impulses whereas in the distal ureter, the antegrade Impulse gradually disappeared and, instead, there were more retrograde Impulses or no activity at all. In this manuscript, a high resolution technique was used to investigate in detail the electrophysiological characteristics of the normal and obstructed ureter in vivo. OBJECTIVE To investigate the propagation of the Electrical Impulses in a unilateral ureteric obstruction model using a high-resolution technique in vivo. MATERIALS AND METHODS In Wistar rats (n= 15), the left mid-ureter was occluded and the Electrical activity was recorded from the proximal and distal part of the obstructed ureter and from the right ureter at different times up to 2 weeks post-obstruction using 64 extracellular electrodes. RESULTS In the left ureter, Impulses propagated in an antegrade direction at a frequency of 15.5 ± 1.3/min and a velocity of 1.6 ± 0.1 cm/s. Immediately post-obstruction, the proximal part showed an increase in frequency (19.1 ± 2.5/min; P < 0.05) followed by a gradual decrease (at 2 weeks: 2.5 ± 1.2/min; P < 0.001). The velocity of these Impulses decreased gradually (at 2 weeks: 0.5 ± 0.1 cm/s; P < 0.05). Distally, the antegrade propagations gradually disappeared and, at 1 week, 33% of ureters showed retrograde Impulses and 67% displayed no Electrical activity. The frequency of both antegrade and retrograde Impulses distal to the obstruction dropped immediately after obstruction so that, at 1 day, it was 1.0 ± 0.3 and 1.5 ± 0.2/min, respectively (P < 0.01 for both). The velocity of these antegrade and retrograde Impulses showed a significant rise throughout the post-obstruction period. The right ureter showed only a transient increase in frequency from 18.7 ± 2.7 to 30.3 ± 6.1/min (P < 0.05). CONCLUSIONS Using this high-resolution technique, it is concluded that, after ureteric obstruction, there were immediate and significant changes in the propagation of Electrical Impulses in the proximal and distal left ureter and in the right ureter, all of which behaved differently. This data may provide a better insight into the electrophysiological function of the normal and obstructed ureter.
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propagation of the Electrical Impulse in reversible unilateral ureteral obstruction as determined at high electrophysiological resolution
The Journal of Urology, 2011Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:Purpose: We investigated the propagation of Electrical Impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo.Materials and Methods: In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded Electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe.Results: Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p <0.05), followed by a 1.4 ± 0.9 per minute decrease (p <0.001). Within the first 2 days after reversal velocity gradually decreased from 1.82 ± 0.12 to 0.79 ± 0.17 cm per second (p <0.001). Release of obstruction gradually restored frequency and velocity, which returned to baseline at 2 weeks. Generally the alterations in rats with complete and partial obstruction were s...
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Propagation of the Electrical Impulse in Reversible Unilateral Ureteral Obstruction as Determined at High Electrophysiological Resolution
The Journal of urology, 2010Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:Purpose: We investigated the propagation of Electrical Impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo.Materials and Methods: In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded Electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe.Results: Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p
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Propagation characteristics of the Electrical Impulse in the normal and obstructed ureter as determined at high electrophysiological resolution.
BJU international, 2010Co-Authors: Fayez T. Hammad, Betty Stephen, Wim J Lammers, Loay LubbadAbstract:To investigate the propagation of the Electrical Impulses in a unilateral ureteric obstruction model using a high-resolution technique in vivo. In Wistar rats (n= 15), the left mid-ureter was occluded and the Electrical activity was recorded from the proximal and distal part of the obstructed ureter and from the right ureter at different times up to 2 weeks post-obstruction using 64 extracellular electrodes. In the left ureter, Impulses propagated in an antegrade direction at a frequency of 15.5 ± 1.3/min and a velocity of 1.6 ± 0.1 cm/s. Immediately post-obstruction, the proximal part showed an increase in frequency (19.1 ± 2.5/min; P < 0.05) followed by a gradual decrease (at 2 weeks: 2.5 ± 1.2/min; P < 0.001). The velocity of these Impulses decreased gradually (at 2 weeks: 0.5 ± 0.1 cm/s; P < 0.05). Distally, the antegrade propagations gradually disappeared and, at 1 week, 33% of ureters showed retrograde Impulses and 67% displayed no Electrical activity. The frequency of both antegrade and retrograde Impulses distal to the obstruction dropped immediately after obstruction so that, at 1 day, it was 1.0 ± 0.3 and 1.5 ± 0.2/min, respectively (P < 0.01 for both). The velocity of these antegrade and retrograde Impulses showed a significant rise throughout the post-obstruction period. The right ureter showed only a transient increase in frequency from 18.7 ± 2.7 to 30.3 ± 6.1/min (P < 0.05). Using this high-resolution technique, it is concluded that, after ureteric obstruction, there were immediate and significant changes in the propagation of Electrical Impulses in the proximal and distal left ureter and in the right ureter, all of which behaved differently. This data may provide a better insight into the electrophysiological function of the normal and obstructed ureter. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.
Fayez T. Hammad - One of the best experts on this subject based on the ideXlab platform.
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Propagation characteristics of the Electrical Impulse in the normal and obstructed ureter as determined at high electrophysiological resolution: Electrical ImpulseS PROPAGATION IN URETERIC OBSTRUCTION
BJU International, 2011Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:What’s known on the subject? and What does the study add? Ureteric obstruction resulted in a differential change in the Electrical activity in the proximal and distal ureter with the proximal ureter having an immediate increase in the frequency of Electrical Impulses whereas in the distal ureter, the antegrade Impulse gradually disappeared and, instead, there were more retrograde Impulses or no activity at all. In this manuscript, a high resolution technique was used to investigate in detail the electrophysiological characteristics of the normal and obstructed ureter in vivo. OBJECTIVE To investigate the propagation of the Electrical Impulses in a unilateral ureteric obstruction model using a high-resolution technique in vivo. MATERIALS AND METHODS In Wistar rats (n= 15), the left mid-ureter was occluded and the Electrical activity was recorded from the proximal and distal part of the obstructed ureter and from the right ureter at different times up to 2 weeks post-obstruction using 64 extracellular electrodes. RESULTS In the left ureter, Impulses propagated in an antegrade direction at a frequency of 15.5 ± 1.3/min and a velocity of 1.6 ± 0.1 cm/s. Immediately post-obstruction, the proximal part showed an increase in frequency (19.1 ± 2.5/min; P < 0.05) followed by a gradual decrease (at 2 weeks: 2.5 ± 1.2/min; P < 0.001). The velocity of these Impulses decreased gradually (at 2 weeks: 0.5 ± 0.1 cm/s; P < 0.05). Distally, the antegrade propagations gradually disappeared and, at 1 week, 33% of ureters showed retrograde Impulses and 67% displayed no Electrical activity. The frequency of both antegrade and retrograde Impulses distal to the obstruction dropped immediately after obstruction so that, at 1 day, it was 1.0 ± 0.3 and 1.5 ± 0.2/min, respectively (P < 0.01 for both). The velocity of these antegrade and retrograde Impulses showed a significant rise throughout the post-obstruction period. The right ureter showed only a transient increase in frequency from 18.7 ± 2.7 to 30.3 ± 6.1/min (P < 0.05). CONCLUSIONS Using this high-resolution technique, it is concluded that, after ureteric obstruction, there were immediate and significant changes in the propagation of Electrical Impulses in the proximal and distal left ureter and in the right ureter, all of which behaved differently. This data may provide a better insight into the electrophysiological function of the normal and obstructed ureter.
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propagation of the Electrical Impulse in reversible unilateral ureteral obstruction as determined at high electrophysiological resolution
The Journal of Urology, 2011Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:Purpose: We investigated the propagation of Electrical Impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo.Materials and Methods: In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded Electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe.Results: Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p <0.05), followed by a 1.4 ± 0.9 per minute decrease (p <0.001). Within the first 2 days after reversal velocity gradually decreased from 1.82 ± 0.12 to 0.79 ± 0.17 cm per second (p <0.001). Release of obstruction gradually restored frequency and velocity, which returned to baseline at 2 weeks. Generally the alterations in rats with complete and partial obstruction were s...
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Propagation of the Electrical Impulse in Reversible Unilateral Ureteral Obstruction as Determined at High Electrophysiological Resolution
The Journal of urology, 2010Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:Purpose: We investigated the propagation of Electrical Impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo.Materials and Methods: In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded Electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe.Results: Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p
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Propagation characteristics of the Electrical Impulse in the normal and obstructed ureter as determined at high electrophysiological resolution.
BJU international, 2010Co-Authors: Fayez T. Hammad, Betty Stephen, Wim J Lammers, Loay LubbadAbstract:To investigate the propagation of the Electrical Impulses in a unilateral ureteric obstruction model using a high-resolution technique in vivo. In Wistar rats (n= 15), the left mid-ureter was occluded and the Electrical activity was recorded from the proximal and distal part of the obstructed ureter and from the right ureter at different times up to 2 weeks post-obstruction using 64 extracellular electrodes. In the left ureter, Impulses propagated in an antegrade direction at a frequency of 15.5 ± 1.3/min and a velocity of 1.6 ± 0.1 cm/s. Immediately post-obstruction, the proximal part showed an increase in frequency (19.1 ± 2.5/min; P < 0.05) followed by a gradual decrease (at 2 weeks: 2.5 ± 1.2/min; P < 0.001). The velocity of these Impulses decreased gradually (at 2 weeks: 0.5 ± 0.1 cm/s; P < 0.05). Distally, the antegrade propagations gradually disappeared and, at 1 week, 33% of ureters showed retrograde Impulses and 67% displayed no Electrical activity. The frequency of both antegrade and retrograde Impulses distal to the obstruction dropped immediately after obstruction so that, at 1 day, it was 1.0 ± 0.3 and 1.5 ± 0.2/min, respectively (P < 0.01 for both). The velocity of these antegrade and retrograde Impulses showed a significant rise throughout the post-obstruction period. The right ureter showed only a transient increase in frequency from 18.7 ± 2.7 to 30.3 ± 6.1/min (P < 0.05). Using this high-resolution technique, it is concluded that, after ureteric obstruction, there were immediate and significant changes in the propagation of Electrical Impulses in the proximal and distal left ureter and in the right ureter, all of which behaved differently. This data may provide a better insight into the electrophysiological function of the normal and obstructed ureter. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.
Betty Stephen - One of the best experts on this subject based on the ideXlab platform.
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Propagation characteristics of the Electrical Impulse in the normal and obstructed ureter as determined at high electrophysiological resolution: Electrical ImpulseS PROPAGATION IN URETERIC OBSTRUCTION
BJU International, 2011Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:What’s known on the subject? and What does the study add? Ureteric obstruction resulted in a differential change in the Electrical activity in the proximal and distal ureter with the proximal ureter having an immediate increase in the frequency of Electrical Impulses whereas in the distal ureter, the antegrade Impulse gradually disappeared and, instead, there were more retrograde Impulses or no activity at all. In this manuscript, a high resolution technique was used to investigate in detail the electrophysiological characteristics of the normal and obstructed ureter in vivo. OBJECTIVE To investigate the propagation of the Electrical Impulses in a unilateral ureteric obstruction model using a high-resolution technique in vivo. MATERIALS AND METHODS In Wistar rats (n= 15), the left mid-ureter was occluded and the Electrical activity was recorded from the proximal and distal part of the obstructed ureter and from the right ureter at different times up to 2 weeks post-obstruction using 64 extracellular electrodes. RESULTS In the left ureter, Impulses propagated in an antegrade direction at a frequency of 15.5 ± 1.3/min and a velocity of 1.6 ± 0.1 cm/s. Immediately post-obstruction, the proximal part showed an increase in frequency (19.1 ± 2.5/min; P < 0.05) followed by a gradual decrease (at 2 weeks: 2.5 ± 1.2/min; P < 0.001). The velocity of these Impulses decreased gradually (at 2 weeks: 0.5 ± 0.1 cm/s; P < 0.05). Distally, the antegrade propagations gradually disappeared and, at 1 week, 33% of ureters showed retrograde Impulses and 67% displayed no Electrical activity. The frequency of both antegrade and retrograde Impulses distal to the obstruction dropped immediately after obstruction so that, at 1 day, it was 1.0 ± 0.3 and 1.5 ± 0.2/min, respectively (P < 0.01 for both). The velocity of these antegrade and retrograde Impulses showed a significant rise throughout the post-obstruction period. The right ureter showed only a transient increase in frequency from 18.7 ± 2.7 to 30.3 ± 6.1/min (P < 0.05). CONCLUSIONS Using this high-resolution technique, it is concluded that, after ureteric obstruction, there were immediate and significant changes in the propagation of Electrical Impulses in the proximal and distal left ureter and in the right ureter, all of which behaved differently. This data may provide a better insight into the electrophysiological function of the normal and obstructed ureter.
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propagation of the Electrical Impulse in reversible unilateral ureteral obstruction as determined at high electrophysiological resolution
The Journal of Urology, 2011Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:Purpose: We investigated the propagation of Electrical Impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo.Materials and Methods: In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded Electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe.Results: Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p <0.05), followed by a 1.4 ± 0.9 per minute decrease (p <0.001). Within the first 2 days after reversal velocity gradually decreased from 1.82 ± 0.12 to 0.79 ± 0.17 cm per second (p <0.001). Release of obstruction gradually restored frequency and velocity, which returned to baseline at 2 weeks. Generally the alterations in rats with complete and partial obstruction were s...
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Propagation of the Electrical Impulse in Reversible Unilateral Ureteral Obstruction as Determined at High Electrophysiological Resolution
The Journal of urology, 2010Co-Authors: Fayez T. Hammad, Wim J. E. P. Lammers, Betty Stephen, Loay LubbadAbstract:Purpose: We investigated the propagation of Electrical Impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo.Materials and Methods: In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded Electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe.Results: Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p
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Propagation characteristics of the Electrical Impulse in the normal and obstructed ureter as determined at high electrophysiological resolution.
BJU international, 2010Co-Authors: Fayez T. Hammad, Betty Stephen, Wim J Lammers, Loay LubbadAbstract:To investigate the propagation of the Electrical Impulses in a unilateral ureteric obstruction model using a high-resolution technique in vivo. In Wistar rats (n= 15), the left mid-ureter was occluded and the Electrical activity was recorded from the proximal and distal part of the obstructed ureter and from the right ureter at different times up to 2 weeks post-obstruction using 64 extracellular electrodes. In the left ureter, Impulses propagated in an antegrade direction at a frequency of 15.5 ± 1.3/min and a velocity of 1.6 ± 0.1 cm/s. Immediately post-obstruction, the proximal part showed an increase in frequency (19.1 ± 2.5/min; P < 0.05) followed by a gradual decrease (at 2 weeks: 2.5 ± 1.2/min; P < 0.001). The velocity of these Impulses decreased gradually (at 2 weeks: 0.5 ± 0.1 cm/s; P < 0.05). Distally, the antegrade propagations gradually disappeared and, at 1 week, 33% of ureters showed retrograde Impulses and 67% displayed no Electrical activity. The frequency of both antegrade and retrograde Impulses distal to the obstruction dropped immediately after obstruction so that, at 1 day, it was 1.0 ± 0.3 and 1.5 ± 0.2/min, respectively (P < 0.01 for both). The velocity of these antegrade and retrograde Impulses showed a significant rise throughout the post-obstruction period. The right ureter showed only a transient increase in frequency from 18.7 ± 2.7 to 30.3 ± 6.1/min (P < 0.05). Using this high-resolution technique, it is concluded that, after ureteric obstruction, there were immediate and significant changes in the propagation of Electrical Impulses in the proximal and distal left ureter and in the right ureter, all of which behaved differently. This data may provide a better insight into the electrophysiological function of the normal and obstructed ureter. © 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.
Carol Ann Remme - One of the best experts on this subject based on the ideXlab platform.
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cardiac sodium channel dys function and inherited arrhythmia syndromes
2018Co-Authors: Carol Ann RemmeAbstract:Normal cardiac sodium channel function is essential for ensuring excitability of myocardial cells and proper conduction of the Electrical Impulse within the heart. Cardiac sodium channel dysfunction is associated with an increased risk of arrhythmias and sudden cardiac death. Over the last 20 years, (combined) genetic, electrophysiological, and molecular studies have provided insight into the (dys)function and (dys)regulation of the cardiac sodium channel under physiological circumstances and in the setting of SCN5A mutations identified in patients with inherited arrhythmia syndromes. Although our understanding of these sodium channelopathies has increased substantially, important issues remain incompletely understood. It has become increasingly clear that sodium channel distribution, function, and regulation are more complicated than traditionally assumed. Moreover, recent evidence suggests that the sodium channel may play additional, as of yet unrecognized, roles in cardiomyocyte function, which in turn may ultimately also impact on arrhythmogenesis. In this chapter, an overview is provided of the structure and function of the cardiac sodium channel and the clinical and biophysical characteristics of inherited sodium channel dysfunction. In addition, more recent insights into the electrophysiological and molecular aspects of sodium channel dysregulation and dysfunction in the setting of SCN5A mutations are discussed.
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review sodium channel dys function and cardiac arrhythmias
Cardiovascular Therapeutics, 2010Co-Authors: Carol Ann Remme, Connie R BezzinaAbstract:SUMMARY Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation and propagation of action potentials throughout the myocardium and consequently plays a central role in excitability of myocardial cells and proper conduction of the Electrical Impulse within the heart. The importance of sodium channels for normal cardiac Electrical activity is emphasized by the occurrence of potentially lethal arrhythmias in the setting of inherited and acquired sodium channel disease. During common pathological conditions such as myocardial ischemia and heart failure, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. In addition, sodium channel dysfunction caused by mutations in the SCN5A gene, encoding the major sodium channel in heart, is associated with a number of arrhythmia syndromes. Here, we provide an overview of the structure and function of the cardiac sodium channel, the clinical and biophysical characteristics of inherited and acquired sodium channel dysfunction, and the (limited) therapeutic options for the treatment of cardiac sodium channel disease.
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sodium channel dys function and cardiac arrhythmias
Cardiovascular Therapeutics, 2010Co-Authors: Carol Ann Remme, Connie R BezzinaAbstract:Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation and propagation of action potentials throughout the myocardium and consequently plays a central role in excitability of myocardial cells and proper conduction of the Electrical Impulse within the heart. The importance of sodium channels for normal cardiac Electrical activity is emphasized by the occurrence of potentially lethal arrhythmias in the setting of inherited and acquired sodium channel disease. During common pathological conditions such as myocardial ischemia and heart failure, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. In addition, sodium channel dysfunction caused by mutations in the SCN5A gene, encoding the major sodium channel in heart, is associated with a number of arrhythmia syndromes. Here, we provide an overview of the structure and function of the cardiac sodium channel, the clinical and biophysical characteristics of inherited and acquired sodium channel dysfunction, and the (limited) therapeutic options for the treatment of cardiac sodium channel disease.
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Abstract 1504: Scn4b Is A Genetic Modifier Of Cardiac Conduction Disease In Mice
Circulation, 2008Co-Authors: Brendon P. Scicluna, Carol Ann Remme, Arie O. Verkerk, Ahmad S. Amin, Michael W.t. Tanck, Leander Beekman, Vera H.m. Deneer, Catherine Chevalier, Fumitaka Oyama, Haruko MiyazakiAbstract:Background: Conduction slowing of the cardiac Electrical Impulse may evoke cardiac arrhythmias that result in sudden cardiac death. We have previously generated a mouse model of cardiac Na+ channel...
Connie R Bezzina - One of the best experts on this subject based on the ideXlab platform.
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review sodium channel dys function and cardiac arrhythmias
Cardiovascular Therapeutics, 2010Co-Authors: Carol Ann Remme, Connie R BezzinaAbstract:SUMMARY Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation and propagation of action potentials throughout the myocardium and consequently plays a central role in excitability of myocardial cells and proper conduction of the Electrical Impulse within the heart. The importance of sodium channels for normal cardiac Electrical activity is emphasized by the occurrence of potentially lethal arrhythmias in the setting of inherited and acquired sodium channel disease. During common pathological conditions such as myocardial ischemia and heart failure, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. In addition, sodium channel dysfunction caused by mutations in the SCN5A gene, encoding the major sodium channel in heart, is associated with a number of arrhythmia syndromes. Here, we provide an overview of the structure and function of the cardiac sodium channel, the clinical and biophysical characteristics of inherited and acquired sodium channel dysfunction, and the (limited) therapeutic options for the treatment of cardiac sodium channel disease.
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sodium channel dys function and cardiac arrhythmias
Cardiovascular Therapeutics, 2010Co-Authors: Carol Ann Remme, Connie R BezzinaAbstract:Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation and propagation of action potentials throughout the myocardium and consequently plays a central role in excitability of myocardial cells and proper conduction of the Electrical Impulse within the heart. The importance of sodium channels for normal cardiac Electrical activity is emphasized by the occurrence of potentially lethal arrhythmias in the setting of inherited and acquired sodium channel disease. During common pathological conditions such as myocardial ischemia and heart failure, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. In addition, sodium channel dysfunction caused by mutations in the SCN5A gene, encoding the major sodium channel in heart, is associated with a number of arrhythmia syndromes. Here, we provide an overview of the structure and function of the cardiac sodium channel, the clinical and biophysical characteristics of inherited and acquired sodium channel dysfunction, and the (limited) therapeutic options for the treatment of cardiac sodium channel disease.