The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.

Mechanisms underlying pacemaker activity in the sinus node remain controversial, with some ascribing a dominant role to timing events in the surface membrane (‘membrane clock’) and others to uptake and release of calcium from the sarcoplasmic reticulum (‘calcium clock’). Here we discuss recent evide...

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Main Authors: Rebecca Anne Capel, Derek Anthony TERRAR
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-03-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00080/full
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spelling doaj-52cf4c541eaf42df87500cb682cd12c12020-11-24T23:39:22ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2015-03-01610.3389/fphys.2015.00080133766The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.Rebecca Anne Capel0Derek Anthony TERRAR1University of OxfordUniversity of OxfordMechanisms underlying pacemaker activity in the sinus node remain controversial, with some ascribing a dominant role to timing events in the surface membrane (‘membrane clock’) and others to uptake and release of calcium from the sarcoplasmic reticulum (‘calcium clock’). Here we discuss recent evidence on mechanisms underlying pacemaker activity with a particular emphasis on the many roles of calcium. There are particular areas of controversy concerning the contribution of calcium spark-like events and the importance of I(f) to spontaneous diastolic depolarisation, though it will be suggested that neither of these is essential for pacemaking. Sodium-calcium exchange (NCX) is most often considered in the context of mediating membrane depolarisation after spark-like events. We present evidence for a broader role of this electrogenic exchanger which need not always depend upon these spark-like events. Short (ms or sec) and long (minutes) term influences of calcium are discussed including direct regulation of ion channels and NCX, and controlling the activity of calcium-dependent enzymes (including CaMKII, AC1 and AC8). The balance between the many contributory factors to pacemaker activity may well alter with experimental and clinical conditions, and potentially redundant mechanisms are desirable to ensure the regular spontaneous heart rate that is essential for life. This review presents evidence that calcium is central to the normal control of pacemaking across a range of temporal scales and seeks to broaden the accepted description of the ‘calcium clock’ to cover these important influences.http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00080/fullCardiacsino-atrial nodecytosolic calciumpacemakingmembrane clockcalcium clock
collection DOAJ
language English
format Article
sources DOAJ
author Rebecca Anne Capel
Derek Anthony TERRAR
spellingShingle Rebecca Anne Capel
Derek Anthony TERRAR
The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.
Frontiers in Physiology
Cardiac
sino-atrial node
cytosolic calcium
pacemaking
membrane clock
calcium clock
author_facet Rebecca Anne Capel
Derek Anthony TERRAR
author_sort Rebecca Anne Capel
title The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.
title_short The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.
title_full The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.
title_fullStr The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.
title_full_unstemmed The importance of Ca2+-dependent mechanisms for the initiation of the heartbeat.
title_sort importance of ca2+-dependent mechanisms for the initiation of the heartbeat.
publisher Frontiers Media S.A.
series Frontiers in Physiology
issn 1664-042X
publishDate 2015-03-01
description Mechanisms underlying pacemaker activity in the sinus node remain controversial, with some ascribing a dominant role to timing events in the surface membrane (‘membrane clock’) and others to uptake and release of calcium from the sarcoplasmic reticulum (‘calcium clock’). Here we discuss recent evidence on mechanisms underlying pacemaker activity with a particular emphasis on the many roles of calcium. There are particular areas of controversy concerning the contribution of calcium spark-like events and the importance of I(f) to spontaneous diastolic depolarisation, though it will be suggested that neither of these is essential for pacemaking. Sodium-calcium exchange (NCX) is most often considered in the context of mediating membrane depolarisation after spark-like events. We present evidence for a broader role of this electrogenic exchanger which need not always depend upon these spark-like events. Short (ms or sec) and long (minutes) term influences of calcium are discussed including direct regulation of ion channels and NCX, and controlling the activity of calcium-dependent enzymes (including CaMKII, AC1 and AC8). The balance between the many contributory factors to pacemaker activity may well alter with experimental and clinical conditions, and potentially redundant mechanisms are desirable to ensure the regular spontaneous heart rate that is essential for life. This review presents evidence that calcium is central to the normal control of pacemaking across a range of temporal scales and seeks to broaden the accepted description of the ‘calcium clock’ to cover these important influences.
topic Cardiac
sino-atrial node
cytosolic calcium
pacemaking
membrane clock
calcium clock
url http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00080/full
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