Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Apr;7(4):559-64.
doi: 10.1016/j.hrthm.2009.12.013. Epub 2009 Dec 24.

A paradigm shift for the heart's pacemaker

Edward G Lakatta  1
Affiliations

A paradigm shift for the heart's pacemaker

Edward G Lakatta. Heart Rhythm. 2010 Apr.
No abstract available

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Schematic illustration of the basal and reserve cardiac pacemaker regulation by cAMP-mediated, PKA-dependent Ca2+ signaling. Step-by-step, detailed explanation of the events depicted within the scheme progressively unfolds within the text.
Fig. 2
Fig. 2
A. The LCR period of the coupled pacemaker clock system. Top--Simultanesouly measured confocal line scan image of sub-sarcolemmal Ca2+ and membrane potential in a representative rabbit SANC. Arrows indicate LCR occurrence during DD. Bottom-- Definition of LCR period and AP cycle length (Modified from 5). B. The relative effects of a specific peptide PKA inhibitor (PKI), carbachol (CCh), phosphodiesterase (PDE) inhibition by milrinone or isobutylmethylxanthine (IBMX), and isoproterenol (ISO) to alter the LCR period are linked to their effects on the phospholamban (PLB) phosphorylation. The dashed line is the best fit least squares logarithmic function through the points: Y=−52.01 ln(X) + 107.11 (R2=0.92). C. The relative effects of PKI, CCh, PDE inhibition and ISO to alter the spontaneous cycle length over a wide range are linked to their effects on the LCR period. The least squares linear function through the points is: cycle length = 0.89 LCR period + 11.43 ms, r2=0.97. The dashed line is the line of identity. D. A novel numerical SANC model of a dynamically integrated system of Ca2+ and membrane clocks predicts the wide range of pacemaker rate modulation via variations in SR Ca2+ pumping rate (color coded, 1 to 30 mM/s), mimicking various degrees of PKA-dependent phospholamban phosphorylation. Shown are simultaneous simulations of SR [Ca2+], SR Ca2+ release flux, INCX, and Vm. Modified from.
See this image and copyright information in PMC

References

    1. Maltsev VA, Vinogradova TM, Lakatta EG. The emergence of a general theory of the initiation and strength of the heartbeat. J Pharmacol Sci. 2006;100:338–369. - PubMed
    1. Vinogradova TM, Lyashkov AE, Zhu W, et al. High basal protein kinase A-dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells. Circ Res. 2006;98:505–514. - PubMed
    1. Vinogradova TM, Zhou YY, Maltsev V, et al. Rhythmic ryanodine receptor Ca2+ releases during diastolic depolarization of sinoatrial pacemaker cells do not require membrane depolarization. Circ Res. 2004;94:802–809. - PubMed
    1. Maltsev VA, Lakatta EG. Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model. Am J Physiol Heart Circ Physiol. 2009;296:H594–H615. - PMC - PubMed
    1. Bogdanov KY, Maltsev VA, Vinogradova TM, et al. Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state. Circ Res. 2006;99:979–987. - PubMed

Publication types