scholarly journals Unique Ca2+-Cycling Protein Abundance and Regulation Sustains Local Ca2+ Releases and Spontaneous Firing of Rabbit Sinoatrial Node Cells

2018 ◽  
Vol 19 (8) ◽  
pp. 2173 ◽  
Author(s):  
Tatiana Vinogradova ◽  
Syevda Tagirova (Sirenko) ◽  
Edward Lakatta
Keyword(s):  
Sinoatrial Node ◽  
Ventricular Myocytes ◽  
Ryanodine Receptors ◽  
Cell Types ◽  
Protein Abundance ◽  
Gradual Change ◽  
Spontaneous Firing ◽  
Diastolic Depolarization ◽  
Sinoatrial Node Cells ◽  
Rabbit Sinoatrial Node

Spontaneous beating of the heart pacemaker, the sinoatrial node, is generated by sinoatrial node cells (SANC) and caused by gradual change of the membrane potential called diastolic depolarization (DD). Submembrane local Ca2+ releases (LCR) from sarcoplasmic reticulum (SR) occur during late DD and activate an inward Na+/Ca2+ exchange current, which accelerates the DD rate leading to earlier occurrence of an action potential. A comparison of intrinsic SR Ca2+ cycling revealed that, at similar physiological Ca2+ concentrations, LCRs are large and rhythmic in permeabilized SANC, but small and random in permeabilized ventricular myocytes (VM). Permeabilized SANC spontaneously released more Ca2+ from SR than VM, despite comparable SR Ca2+ content in both cell types. In this review we discuss specific patterns of expression and distribution of SR Ca2+ cycling proteins (SR Ca2+ ATPase (SERCA2), phospholamban (PLB) and ryanodine receptors (RyR)) in SANC and ventricular myocytes. We link ability of SANC to generate larger and rhythmic LCRs with increased abundance of SERCA2, reduced abundance of the SERCA inhibitor PLB. In addition, an increase in intracellular [Ca2+] increases phosphorylation of both PLB and RyR exclusively in SANC. The differences in SR Ca2+ cycling protein expression between SANC and VM provide insights into diverse regulation of intrinsic SR Ca2+ cycling that drives automaticity of SANC.

scholarly journals The Anti-Cancer Drug Vatalanib (Ptk787/Zk222584) Suppresses Normal Spontaneous Firing of Rabbit Sinoatrial Node Cells (SANC)

2019 ◽  
Vol 116 (3) ◽  
pp. 385a
Author(s):  
Tatiana M. Vinogradova ◽  
Kirill V. Tarasov ◽  
Yelena S. Tarasova ◽  
Edward G. Lakatta
Keyword(s):  
Sinoatrial Node ◽  
Cancer Drug ◽  
Spontaneous Firing ◽  
Anti Cancer ◽  
Sinoatrial Node Cells ◽  
Rabbit Sinoatrial Node

scholarly journals CaMKII-dependent phosphorylation regulates basal cardiac pacemaker function via modulation of local Ca2+ releases

2016 ◽  
Vol 311 (3) ◽  
pp. H532-H544 ◽  
Author(s):  
Yue Li ◽  
Syevda Sirenko ◽  
Daniel R. Riordon ◽  
Dongmei Yang ◽  
Harold Spurgeon ◽  
...  
Keyword(s):  
Protein Phosphorylation ◽  
Sinoatrial Node ◽  
Ventricular Myocytes ◽  
Ryanodine Receptors ◽  
Cardiac Pacemaker ◽  
Gradual Change ◽  
Pacemaker Function ◽  
Dependent Protein ◽  
Highly Correlated ◽  
Camkii Activation

Spontaneous beating of the heart pacemaker, the sinoatrial node, is generated by sinoatrial node cells (SANC) due to gradual change of the membrane potential called diastolic depolarization (DD). Spontaneous, submembrane local Ca2+ releases (LCR) from ryanodine receptors (RyR) occur during late DD and activate an inward Na+/Ca2+exchange current to boost the DD rate and fire an action potential (AP). Here we studied the extent of basal Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation and the role of basal CaMKII-dependent protein phosphorylation in generation of LCRs and regulation of normal automaticity of intact rabbit SANC. The basal level of activated (autophosphorylated) CaMKII in rabbit SANC surpassed that in ventricular myocytes (VM) by approximately twofold, and this was accompanied by high basal level of protein phosphorylation. Specifically, phosphorylation of phospholamban (PLB) at the CaMKII-dependent Thr17 site was approximately threefold greater in SANC compared with VM, and RyR phosphorylation at CaMKII-dependent Ser2815 site was ∼10-fold greater in the SA node, compared with that in ventricle. CaMKII inhibition reduced phosphorylation of PLB and RyR, decreased LCR size, increased LCR periods (time from AP-induced Ca2+ transient to subsequent LCR), and suppressed spontaneous SANC firing. Graded changes in CaMKII-dependent phosphorylation (indexed by PLB phosphorylation at the Thr17site) produced by CaMKII inhibition, β-AR stimulation or phosphodiesterase inhibition were highly correlated with changes in SR Ca2+ replenishment times and LCR periods and concomitant changes in spontaneous SANC cycle lengths ( R2 = 0.96). Thus high basal CaMKII activation modifies the phosphorylation state of Ca2+ cycling proteins PLB, RyR, L-type Ca2+ channels (and likely others), adjusting LCR period and characteristics, and ultimately regulates both normal and reserve cardiac pacemaker function.

scholarly journals Basal Spontaneous Firing of Rabbit Sinoatrial Node Cells Is Regulated by Dual Activation of PDEs (Phosphodiesterases) 3 and 4

2018 ◽  
Vol 11 (6) ◽  
Author(s):  
Tatiana M. Vinogradova ◽  
Syevda Sirenko ◽  
Yevgeniya O. Lukyanenko ◽  
Dongmei Yang ◽  
Kirill V. Tarasov ◽  
...  
Keyword(s):  
Sinoatrial Node ◽  
Spontaneous Firing ◽  
Sinoatrial Node Cells ◽  
Dual Activation ◽  
Rabbit Sinoatrial Node

scholarly journals Electrophysiological analysis of the negative chronotropic effect of endothelin‐1 in rabbit sinoatrial node cells

2001 ◽  
Vol 537 (2) ◽  
pp. 467-488 ◽  
Author(s):  
Kageyoshi Ono ◽  
Haruko Masumiya ◽  
Aiji Sakamoto ◽  
Georges Christé ◽  
Toshinori Shijuku ◽  
...  
Keyword(s):  
Sinoatrial Node ◽  
Chronotropic Effect ◽  
Endothelin 1 ◽  
Negative Chronotropic Effect ◽  
Electrophysiological Analysis ◽  
Sinoatrial Node Cells ◽  
Rabbit Sinoatrial Node

Ionic Currents in Rabbit Sinoatrial Node Cells

1978 ◽  
pp. 301-310 ◽  
Author(s):  
Akinori Noma ◽  
Kaoru Yanagihara ◽  
Hiroshi Irisawa
Keyword(s):  
Sinoatrial Node ◽  
Ionic Currents ◽  
Sinoatrial Node Cells ◽  
Rabbit Sinoatrial Node

scholarly journals Concurrent PDE3 and PDE4 Activation Suppresses Local Ca2+ Releases (LCR) to Regulate Normal Spontaneous Firing of Sinoatrial Node Cells (SANC)

2016 ◽  
Vol 110 (3) ◽  
pp. 273a-274a
Author(s):  
Tatiana M. Vinogradova ◽  
Yevgeniya Lukyanenko ◽  
Kirill V. Tarasov ◽  
Syevda Sirenko ◽  
Alexey E. Lyashkov ◽  
...  
Keyword(s):  
Sinoatrial Node ◽  
Spontaneous Firing ◽  
Sinoatrial Node Cells

A rapidly activating delayed rectifier K+ channel in rabbit sinoatrial node cells

1995 ◽  
Vol 269 (2) ◽  
pp. H443-H452 ◽  
Author(s):  
H. Ito ◽  
K. Ono
Keyword(s):  
Steady State ◽  
Sinoatrial Node ◽  
Single Channel ◽  
Ensemble Average ◽  
Negative Slope ◽  
Delayed Rectifier ◽  
Channel Current ◽  
Single Channel Current ◽  
Sinoatrial Node Cells ◽  
Rabbit Sinoatrial Node

The single-channel current of the delayed rectifier K+ current (IK) was recorded in rabbit sinoatrial node cells. In the cell-attached patch, depolarization from -70 mV to potentials more positive than -50 mV activated the IK channel while repolarization deactivated it. The single-channel conductance was 7.8 pS for the outward current and 10.8 pS for the inward current (n = 6). The steady-state open probability (NPo) was maximum at around -30 mV and markedly decreased at more positive potentials. On repolarization from positive potentials, the channel was initially closed and then rapidly opened. The ensemble average showed an initial rise to a peak followed by the deactivation time course. Because the channel events were completely blocked by E-4031, the drug-sensitive component was examined in the whole cell current. The steady-state current-voltage relation of the drug-sensitive current showed a marked negative slope at potentials more positive than -10 mV. Upon repolarization, the drug-sensitive current initially increased (removal of inactivation) to the peak of the outward tail current, which was in agreement with the ensemble average of the single-channel current. We conclude that IK in the sinoatrial node cells is largely composed of the rapidly activating IK (IK,r) channels and that the inward rectification of IK,r, which is more marked than had been assumed in previous studies, is due to the decrease in NPo.

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