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...
Main Authors: | , |
---|---|
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 |
id |
doaj-52cf4c541eaf42df87500cb682cd12c1 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT rebeccaannecapel theimportanceofca2dependentmechanismsfortheinitiationoftheheartbeat AT derekanthonyterrar theimportanceofca2dependentmechanismsfortheinitiationoftheheartbeat AT rebeccaannecapel importanceofca2dependentmechanismsfortheinitiationoftheheartbeat AT derekanthonyterrar importanceofca2dependentmechanismsfortheinitiationoftheheartbeat |
_version_ |
1725514046363402240 |