Abstract
Although the ensemble of voltage- and time-dependent rhythms of surface membrane ion channels, the membrane "Clock", is the immediate cause of a sinoatrial nodal cell (SANC) action potential (AP), it does not necessarily follow that this ion channel ensemble is the formal cause of spontaneous, rhythmic APs. SANC also generates intracellular oscillatory spontaneous Ca 2+ releases that ignite excitation (SCaRIE) of the surface membrane via Na+/Ca2+ exchanger activation. The idea that a rhythmic intracellular Ca2+ Clock might keep time for normal automaticity of SANC, however, has not been assimilated into mainstream pacemaker dogma. Recent experimental evidence, derived from simultaneous, confocal imaging of submembrane Ca2+ and membrane potential of SANC, and supported by numerical modeling, indicates that normal automaticity of SANC is entrained and stabilized by the tight integration of the SR Ca2+ Clock that generates rhythmic SCaRIE, and the surface membrane Clock that responds to SCaRIE to immediately produce APs of an adequate shape. Thus, tightly controlled, rhythmic SCaRIE does not merely fine tune SANC AP firing, but is the formal cause of the basal and reserve rhythms, insuring pacemaker stability by rhythmically integrating multiple Ca2+-dependent functions, and effects normal automaticity by rhythmic ignition of the surface membrane Clock.
| Original language | English (US) |
|---|---|
| Title of host publication | Interactive and Integrative Cardiology |
| Pages | 178-206 |
| Number of pages | 29 |
| Volume | 1080 |
| DOIs | |
| State | Published - Oct 2006 |
| Externally published | Yes |
Publication series
| Name | Annals of the New York Academy of Sciences |
|---|---|
| Volume | 1080 |
| ISSN (Print) | 00778923 |
| ISSN (Electronic) | 17496632 |
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Keywords
- Cardiac pacemaker
- Na /Ca exchanger
- Normal automaticity
- Ryanodine receptor
- Sarcoplasmic reticulum
- Spontaneous local Ca release
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- History and Philosophy of Science
Cite this
The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker. / Lakatta, Edward; Vinogradova, Tatiana; Lyashkov, Alexey; Sirenko, Syevda; Zhu, Weizong; Ruknudin, Abdul; Maltsev, Victor A.
Interactive and Integrative Cardiology. Vol. 1080 2006. p. 178-206 (Annals of the New York Academy of Sciences; Vol. 1080).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker
AU - Lakatta, Edward
AU - Vinogradova, Tatiana
AU - Lyashkov, Alexey
AU - Sirenko, Syevda
AU - Zhu, Weizong
AU - Ruknudin, Abdul
AU - Maltsev, Victor A.
PY - 2006/10
Y1 - 2006/10
N2 - Although the ensemble of voltage- and time-dependent rhythms of surface membrane ion channels, the membrane "Clock", is the immediate cause of a sinoatrial nodal cell (SANC) action potential (AP), it does not necessarily follow that this ion channel ensemble is the formal cause of spontaneous, rhythmic APs. SANC also generates intracellular oscillatory spontaneous Ca 2+ releases that ignite excitation (SCaRIE) of the surface membrane via Na+/Ca2+ exchanger activation. The idea that a rhythmic intracellular Ca2+ Clock might keep time for normal automaticity of SANC, however, has not been assimilated into mainstream pacemaker dogma. Recent experimental evidence, derived from simultaneous, confocal imaging of submembrane Ca2+ and membrane potential of SANC, and supported by numerical modeling, indicates that normal automaticity of SANC is entrained and stabilized by the tight integration of the SR Ca2+ Clock that generates rhythmic SCaRIE, and the surface membrane Clock that responds to SCaRIE to immediately produce APs of an adequate shape. Thus, tightly controlled, rhythmic SCaRIE does not merely fine tune SANC AP firing, but is the formal cause of the basal and reserve rhythms, insuring pacemaker stability by rhythmically integrating multiple Ca2+-dependent functions, and effects normal automaticity by rhythmic ignition of the surface membrane Clock.
AB - Although the ensemble of voltage- and time-dependent rhythms of surface membrane ion channels, the membrane "Clock", is the immediate cause of a sinoatrial nodal cell (SANC) action potential (AP), it does not necessarily follow that this ion channel ensemble is the formal cause of spontaneous, rhythmic APs. SANC also generates intracellular oscillatory spontaneous Ca 2+ releases that ignite excitation (SCaRIE) of the surface membrane via Na+/Ca2+ exchanger activation. The idea that a rhythmic intracellular Ca2+ Clock might keep time for normal automaticity of SANC, however, has not been assimilated into mainstream pacemaker dogma. Recent experimental evidence, derived from simultaneous, confocal imaging of submembrane Ca2+ and membrane potential of SANC, and supported by numerical modeling, indicates that normal automaticity of SANC is entrained and stabilized by the tight integration of the SR Ca2+ Clock that generates rhythmic SCaRIE, and the surface membrane Clock that responds to SCaRIE to immediately produce APs of an adequate shape. Thus, tightly controlled, rhythmic SCaRIE does not merely fine tune SANC AP firing, but is the formal cause of the basal and reserve rhythms, insuring pacemaker stability by rhythmically integrating multiple Ca2+-dependent functions, and effects normal automaticity by rhythmic ignition of the surface membrane Clock.
KW - Cardiac pacemaker
KW - Na /Ca exchanger
KW - Normal automaticity
KW - Ryanodine receptor
KW - Sarcoplasmic reticulum
KW - Spontaneous local Ca release
UR - http://www.scopus.com/inward/record.url?scp=33845667862&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845667862&partnerID=8YFLogxK
U2 - 10.1196/annals.1380.016
DO - 10.1196/annals.1380.016
M3 - Conference contribution
C2 - 17132784
AN - SCOPUS:33845667862
SN - 1573316512
SN - 9781573316514
VL - 1080
T3 - Annals of the New York Academy of Sciences
SP - 178
EP - 206
BT - Interactive and Integrative Cardiology
ER -