Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge

<p>Abstract</p> <p>Background</p> <p>The diastolic oscillatory after-potential V<sub>os </sub>and pre-potential ThV<sub>os </sub>play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate...

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Main Authors: Vassalle Mario, Catanzaro John, Nett Michael, Rota Marcello
Format: Article
Language:English
Published: BMC 2009-01-01
Series:Journal of Biomedical Science
Online Access:http://www.jbiomedsci.com/content/16/1/101
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author Vassalle Mario
Catanzaro John
Nett Michael
Rota Marcello
author_facet Vassalle Mario
Catanzaro John
Nett Michael
Rota Marcello
author_sort Vassalle Mario
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The diastolic oscillatory after-potential V<sub>os </sub>and pre-potential ThV<sub>os </sub>play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate whether these oscillatory potentials are also involved in adrenergic control of SAN discharge.</p> <p>Methods</p> <p>V<sub>os </sub>and ThV<sub>os </sub>were visualized by superfusing guinea pig SAN in high [K<sup>+</sup>]<sub>o</sub>. The actions of adrenergic agonists on oscillatory potentials were studied by means of a microelectrode technique. Statistical significance was determined by means of Student's paired <it>t</it>-test.</p> <p>Results</p> <p>In non-spontaneous SAN, norepinephrine (NE) decreased the resting potential into a voltage range ("oscillatory zone") where increasingly larger ThV<sub>os </sub>appeared and initiated spontaneous discharge. In slowly discharging SAN, NE gradually increased the rate by increasing the amplitude and slope of earlier-occurring ThV<sub>os </sub>and of V<sub>os </sub>until these oscillations fused with initial diastolic depolarization (DD<sub>1</sub>). In the presence of NE, sudden fast rhythms were initiated by large V<sub>os </sub>that entered a more negative oscillatory zone and initiated a large ThV<sub>os</sub>. Recovery from NE exposure involved the converse changes. The &#946;-adrenergic agonist isoproterenol had similar actions. Increasing calcium load by decreasing high [K<sup>+</sup>]<sub>o</sub>, by fast drive or by recovery in Tyrode solution led to growth of V<sub>os </sub>and ThV<sub>os </sub>which abruptly fused when a fast sudden rhythm was induced. Low [Ca<sup>2+</sup>]<sub>o </sub>antagonized the adrenergic actions. Cesium (a blocker of I<sub>f</sub>) induced spontaneous discharge in quiescent SAN through ThV<sub>os</sub>. In spontaneous SAN, Cs<sup>+</sup>increased V<sub>os </sub>and ThV<sub>os</sub>, thereby increasing the rate. Cs<sup>+ </sup>did not hinder the positive chronotropic action of NE. Barium increased the rate, as Cs<sup>+ </sup>did.</p> <p>Conclusion</p> <p>Adrenergic agonists: (i) initiate SAN discharge by decreasing the resting potential and inducing ThV<sub>os</sub>; (ii) gradually accelerate SAN rate by predominantly increasing size and slope of earlier and more negative ThV<sub>os</sub>; (iii) can induce sudden fast rhythms through the abrupt fusion of large V<sub>os </sub>with large ThV<sub>os</sub>; (iv) increase V<sub>os </sub>and ThV<sub>os</sub>by increasing cellular calcium; and (v) do not modify the oscillatory potentials by means of the hyperpolarization-activated current I<sub>f</sub>. The results provide evidence for novel mechanisms by which the SAN dominant pacemaker activity is initiated and enhanced by adrenergic agonists.</p>
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spelling doaj.art-982ce11eb45441e7b446deb46b228b782022-12-22T03:10:50ZengBMCJournal of Biomedical Science1021-77701423-01272009-01-01161101Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node dischargeVassalle MarioCatanzaro JohnNett MichaelRota Marcello<p>Abstract</p> <p>Background</p> <p>The diastolic oscillatory after-potential V<sub>os </sub>and pre-potential ThV<sub>os </sub>play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate whether these oscillatory potentials are also involved in adrenergic control of SAN discharge.</p> <p>Methods</p> <p>V<sub>os </sub>and ThV<sub>os </sub>were visualized by superfusing guinea pig SAN in high [K<sup>+</sup>]<sub>o</sub>. The actions of adrenergic agonists on oscillatory potentials were studied by means of a microelectrode technique. Statistical significance was determined by means of Student's paired <it>t</it>-test.</p> <p>Results</p> <p>In non-spontaneous SAN, norepinephrine (NE) decreased the resting potential into a voltage range ("oscillatory zone") where increasingly larger ThV<sub>os </sub>appeared and initiated spontaneous discharge. In slowly discharging SAN, NE gradually increased the rate by increasing the amplitude and slope of earlier-occurring ThV<sub>os </sub>and of V<sub>os </sub>until these oscillations fused with initial diastolic depolarization (DD<sub>1</sub>). In the presence of NE, sudden fast rhythms were initiated by large V<sub>os </sub>that entered a more negative oscillatory zone and initiated a large ThV<sub>os</sub>. Recovery from NE exposure involved the converse changes. The &#946;-adrenergic agonist isoproterenol had similar actions. Increasing calcium load by decreasing high [K<sup>+</sup>]<sub>o</sub>, by fast drive or by recovery in Tyrode solution led to growth of V<sub>os </sub>and ThV<sub>os </sub>which abruptly fused when a fast sudden rhythm was induced. Low [Ca<sup>2+</sup>]<sub>o </sub>antagonized the adrenergic actions. Cesium (a blocker of I<sub>f</sub>) induced spontaneous discharge in quiescent SAN through ThV<sub>os</sub>. In spontaneous SAN, Cs<sup>+</sup>increased V<sub>os </sub>and ThV<sub>os</sub>, thereby increasing the rate. Cs<sup>+ </sup>did not hinder the positive chronotropic action of NE. Barium increased the rate, as Cs<sup>+ </sup>did.</p> <p>Conclusion</p> <p>Adrenergic agonists: (i) initiate SAN discharge by decreasing the resting potential and inducing ThV<sub>os</sub>; (ii) gradually accelerate SAN rate by predominantly increasing size and slope of earlier and more negative ThV<sub>os</sub>; (iii) can induce sudden fast rhythms through the abrupt fusion of large V<sub>os </sub>with large ThV<sub>os</sub>; (iv) increase V<sub>os </sub>and ThV<sub>os</sub>by increasing cellular calcium; and (v) do not modify the oscillatory potentials by means of the hyperpolarization-activated current I<sub>f</sub>. The results provide evidence for novel mechanisms by which the SAN dominant pacemaker activity is initiated and enhanced by adrenergic agonists.</p>http://www.jbiomedsci.com/content/16/1/101
spellingShingle Vassalle Mario
Catanzaro John
Nett Michael
Rota Marcello
Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge
Journal of Biomedical Science
title Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge
title_full Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge
title_fullStr Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge
title_full_unstemmed Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge
title_short Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge
title_sort essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino atrial node discharge
url http://www.jbiomedsci.com/content/16/1/101
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AT nettmichael essentialroleofdiastolicoscillatorypotentialsinadrenergiccontrolofguineapigsinoatrialnodedischarge
AT rotamarcello essentialroleofdiastolicoscillatorypotentialsinadrenergiccontrolofguineapigsinoatrialnodedischarge