CaMKIIδC slows [Ca]i decline in cardiac myocytes by promoting Ca sparks

Tao Guo, Tong Zhang, Kenneth S Ginsburg, Shikha Mishra, Joan Heller Brown, Donald M Bers

Research output: Contribution to journalArticle

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Abstract

Acute activation of calcium/calmodulin-dependent protein kinase (CaMKII) in permeabilized phospholamban knockout (PLN-KO) mouse myocytes phosphorylates ryanodine receptors (RyRs) and activates spontaneous local sarcoplasmic reticulum (SR) Ca release events (Ca sparks) even at constant SR Ca load. To assess how CaMKII regulates SR Ca release in intact myocytes (independent of SR Ca content changes or PLN effects), we compared Ca sparks in PLN-KO versus mice, which also have transgenic cardiac overexpression of CaMKIIδC in the PLN-KO background (KO/TG). Compared with PLN-KO mice, these KO/TG cardiomyocytes exhibited 1), increased twitch Ca transient and fractional release (both by ∼35%), but unaltered SR Ca load; 2), increased resting Ca spark frequency (300%) despite a lower diastolic [Ca]i, which also slowed twitch [Ca]i decline (suggesting CaMKII-dependent RyR Ca sensitization); 3), elevated Ca spark amplitude and rate of Ca release (which might indicate that more RyR channels participate in a single spark); 4), prolonged Ca spark rise time (which implies that CaMKII either delays RyR closure or prolongs the time when openings can occur); 5), more frequent repetitive sparks at single release sites. Analysis of repetitive sparks from individual Ca release sites indicates that CaMKII enhanced RyR Ca sensitivity, but did not change the time course of SR Ca refilling. These results demonstrate that there are dramatic CaMKII-mediated effects on RyR Ca release that occur via regulation of both RyR activation and termination processes.

Original languageEnglish (US)
Pages (from-to)2461-2470
Number of pages10
JournalBiophysical Journal
Volume102
Issue number11
DOIs
StatePublished - Jun 6 2012

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Sarcoplasmic Reticulum
Cardiac Myocytes
Knockout Mice
Muscle Cells
Calcium-Calmodulin-Dependent Protein Kinases
Ryanodine Receptor Calcium Release Channel
phospholamban

ASJC Scopus subject areas

  • Biophysics

Cite this

CaMKIIδC slows [Ca]i decline in cardiac myocytes by promoting Ca sparks. / Guo, Tao; Zhang, Tong; Ginsburg, Kenneth S; Mishra, Shikha; Brown, Joan Heller; Bers, Donald M.

In: Biophysical Journal, Vol. 102, No. 11, 06.06.2012, p. 2461-2470.

Research output: Contribution to journalArticle

Guo, T, Zhang, T, Ginsburg, KS, Mishra, S, Brown, JH & Bers, DM 2012, 'CaMKIIδC slows [Ca]i decline in cardiac myocytes by promoting Ca sparks', Biophysical Journal, vol. 102, no. 11, pp. 2461-2470. https://doi.org/10.1016/j.bpj.2012.04.015
Guo, Tao ; Zhang, Tong ; Ginsburg, Kenneth S ; Mishra, Shikha ; Brown, Joan Heller ; Bers, Donald M. / CaMKIIδC slows [Ca]i decline in cardiac myocytes by promoting Ca sparks. In: Biophysical Journal. 2012 ; Vol. 102, No. 11. pp. 2461-2470.
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