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The Integration of Spontaneous Intracellular Ca 2+ Cycling and Surface Membrane Ion Channel Activation Entrains Normal Automaticity in Cells of the Heart's Pacemaker
Author(s) -
LAKATTA EDWARD G.,
VINOGRADOVA TATIANA,
LYASHKOV ALEXEY,
SIRENKO SYEVDA,
ZHU WEIZONG,
RUKNUDIN ABDUL,
MALTSEV VICTOR A.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1380.016
Subject(s) - biophysics , intracellular , cardiac pacemaker , ion channel , membrane potential , automaticity , chemistry , pacemaker potential , sinoatrial node , neuroscience , microbiology and biotechnology , biology , endocrinology , biochemistry , receptor , heart rate , cognition , blood pressure
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 + /Ca 2+ exchanger activation. The idea that a rhythmic intracellular Ca 2+ 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 Ca 2+ 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 Ca 2+ 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 Ca 2+ ‐dependent functions, and effects normal automaticity by rhythmic ignition of the surface membrane Clock.