The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker

Edward Lakatta, Tatiana Vinogradova, Alexey Lyashkov, Syevda Sirenko, Weizong Zhu, Abdul Ruknudin, Victor A. Maltsev

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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 languageEnglish (US)
Title of host publicationInteractive and Integrative Cardiology
Pages178-206
Number of pages29
Volume1080
DOIs
StatePublished - Oct 2006
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1080
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Pacemakers
Ion Channels
Chemical activation
Clocks
Membranes
Action Potentials
Ion exchangers
Membrane Potentials
Ignition
Automaticity
Cells
Activation
Cycling
Membrane
Clock
Imaging techniques
Electric potential
Causes

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

Lakatta, E., Vinogradova, T., Lyashkov, A., Sirenko, S., Zhu, W., Ruknudin, A., & Maltsev, V. A. (2006). The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker. In Interactive and Integrative Cardiology (Vol. 1080, pp. 178-206). (Annals of the New York Academy of Sciences; Vol. 1080). https://doi.org/10.1196/annals.1380.016

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 proceedingConference contribution

Lakatta, E, Vinogradova, T, Lyashkov, A, Sirenko, S, Zhu, W, Ruknudin, A & Maltsev, VA 2006, The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker. in Interactive and Integrative Cardiology. vol. 1080, Annals of the New York Academy of Sciences, vol. 1080, pp. 178-206. https://doi.org/10.1196/annals.1380.016
Lakatta E, Vinogradova T, Lyashkov A, Sirenko S, Zhu W, Ruknudin A et al. The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker. In Interactive and Integrative Cardiology. Vol. 1080. 2006. p. 178-206. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1380.016
Lakatta, Edward ; Vinogradova, Tatiana ; Lyashkov, Alexey ; Sirenko, Syevda ; Zhu, Weizong ; Ruknudin, Abdul ; Maltsev, Victor A. / The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker. Interactive and Integrative Cardiology. Vol. 1080 2006. pp. 178-206 (Annals of the New York Academy of Sciences).
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