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Cited by 368

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Sinoatrial Nodal Cell Ryanodine Receptor and Na + -Ca 2+ Exchanger: Molecular Partners in Pacemaker Regulation

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Bogdanov, Konstantin Y., Vinogradova, Tatiana M., Lakatta, Edward G.·2001·Circulation Research
DOI 10.1161/hh1201.092095
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Abstract

Abstract —The rate of spontaneous diastolic depolarization (DD) of sinoatrial nodal cells (SANCs) that triggers recurrent action potentials (APs) is a fundamental aspect of the heart’s pacemaker. Here, in experiments on isolated SANCs, using confocal microscopy combined with a patch clamp technique, we show that ryanodine receptor Ca 2+ release during the DD produces a localized subsarcolemmal Ca 2+ increase that spreads in a wavelike manner by Ca 2+ -induced Ca 2+ release and produces an inward current via the Na + -Ca 2+ exchanger (NCX). Ryanodine, a blocker of the sarcoplasmic reticulum Ca 2+ release channel, in a dose-dependent manner reduces the SANC beating rate with an IC 50 of 2.6 μmol/L and abolishes the local Ca 2+ transients that precede the AP upstroke. In voltage-clamped cells in which the DD was simulated by voltage ramp, 3 μmol/L ryanodine decreased an inward current during the voltage ramp by 1.6±0.3 pA/pF (SEM, n=4) leaving the peak of L-type Ca 2+ current unchanged. Likewise, acute blockade of the NCX (via rapid substitution of bath Na + by Li + ) abolished SANC beating and reduced the inward current to a similar extent (1.7±0.4 pA/pF, n=4), as did ryanodine. Thus, in addition to activation/inactivation of multiple ion channels, Ca 2+ activation of the NCX, because of localized sarcoplasmic reticulum Ca 2+ release, is a critical element in a chain of molecular interactions that permits the heartbeat to occur and determines its beating rate.

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Metadata

Authors
Bogdanov, K. Y., Vinogradova, T. M., & Lakatta, E. G.
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2001-06-22
Volume
88
Issue
12
Pages
1254-1258
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/hh1201.092095
OpenAlex
W1996022889
Cited by
368
References
20
FWCI
8.62
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Sinoatrial Nodal Cell Ryanodine Receptor and Na + -Ca 2+ Exchanger: Molecular Partners in Pacemaker Regulation. https://app.cochat.ai/papers/10.1161/hh1201.092095
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Bogdanov, K. Y., Vinogradova, T. M., & Lakatta, E. G. (2001). Sinoatrial Nodal Cell Ryanodine Receptor and Na + -Ca 2+ Exchanger: Molecular Partners in Pacemaker Regulation. Circulation Research. https://doi.org/10.1161/hh1201.092095

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