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10.1161/CIRCRESAHA.114.302505

http://scihub22266oqcxt.onion/10.1161/CIRCRESAHA.114.302505
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C4000583!4000583!24568740
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suck abstract from ncbi


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pmid24568740      Circ+Res 2014 ; 114 (9): 1410-21
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  • Optical Mapping of Sarcoplasmic Reticulum Ca2+ in the Intact Heart: Ryanodine Receptor Refractoriness During Alternans and Fibrillation #MMPMID24568740
  • Wang L; Myles RC; De Jesus NM; Ohlendorf AK; Bers DM; Ripplinger CM
  • Circ Res 2014[Apr]; 114 (9): 1410-21 PMID24568740show ga
  • Rationale: Sarcoplasmic reticulum (SR) Ca2+ cycling is key to normal excitation-contraction coupling but may also contribute to pathological cardiac alternans and arrhythmia. Objective: To measure intra-SR free [Ca2+] ([Ca2+]SR) changes in intact hearts during alternans and ventricular fibrillation (VF). Methods and Results: Simultaneous optical mapping of Vm (with RH237) and [Ca2+]SR (with Fluo-5N AM) was performed in Langendorff-perfused rabbit hearts. Alternans and VF were induced by rapid pacing. SR Ca2+ and action potential duration (APD) alternans occurred in-phase, but SR Ca2+ alternans emerged first as cycle length was progressively reduced (217±10ms vs. 190±13ms, p<0.05). Ryanodine receptor (RyR) refractoriness played a key role in the onset of SR Ca2+ alternans, with SR Ca2+ release alternans routinely occurring without changes in diastolic [Ca2+]SR. Sensitizing RyR with caffeine (200?M) significantly reduced the pacing threshold for both SR Ca2+ and APD alternans (188±15ms and 173±12ms, p<0.05 vs. baseline). Caffeine also reduced the magnitude of spatially discordant SR Ca2+ alternans, but not APD alternans, the pacing threshold for discordance, or threshold for VF. During VF, [Ca2+]SR was high, but RyR remained nearly continuously refractory, resulting in minimal SR Ca2+ release throughout VF. Conclusions: In intact hearts RyR refractoriness initiates SR Ca2+ release alternans, that can be amplified by diastolic [Ca2+]SR alternans and lead to APD alternans. Sensitizing RyR suppresses spatially concordant, but not discordant SR Ca2+ and APD alternans. Despite increased [Ca2+]SR during VF, SR Ca2+ release was nearly continuously refractory. This novel method provides insight into SR Ca2+ handling during cardiac alternans and arrhythmia.
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