Journal
CARDIOVASCULAR RESEARCH
Volume 104, Issue 2, Pages 347-354Publisher
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvu201
Keywords
Calcium; Buffering; SERCA; Troponin; Phospholamban
Categories
Funding
- British Heart Foundation [PG/09/062/27872, PG/12/89/29970, PG/10/89/28630, PG/08/078/25593, FS/10/71/28563, FS/09/036/27823, PG/11/16/28777, FS/09/002/26487, FS/12/57/29717] Funding Source: researchfish
- British Heart Foundation [FS/09/002, PG/08/078/25593, FS/12/57/29717, FS/09/036/27823, FS/10/71/28563, PG/11/16, PG/09/062/27872, PG/10/89/28630, PG/12/89/29970, PG/11/16/28777, FS/12/57, CH/2000/04, FS/09/002/26487] Funding Source: Medline
- NHLBI NIH HHS [P01 HL 062426, P01 HL062426, R01 HL 022231] Funding Source: Medline
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During activation of cardiac myocytes, less than 1% of cytosolic Ca is free; the rest is bound to buffers, largely SERCA, and troponin C. Signalling by phosphorylation, as occurs during beta-adrenergic stimulation, changes the Ca-binding affinity of these proteins and may affect the systolic Ca transient. Our aim was to determine the effects of beta-adrenergic stimulation on Ca buffering and to differentiate between the roles of SERCA and troponin. Ca buffering was studied in cardiac myocytes from mice: wild-type (WT), phospholamban-knockout (PLN-KO), and mice expressing slow skeletal troponin I (ssTnI) that is not protein kinase A phosphorylatable. WT cells showed no change in Ca buffering in response to the beta-adrenoceptor agonist isoproterenol (ISO). However, ISO decreased Ca buffering in PLN-KO myocytes, presumably unmasking the role of troponin. This effect was confirmed in WT cells in which SERCA activity was blocked with the application of thapsigargin. In contrast, ISO increased Ca buffering in ssTnI cells, presumably revealing the effect of an increase in Ca binding to SERCA. These data indicate the individual roles played by SERCA and troponin in Ca buffering during beta-adrenergic stimulation and that these two buffers effectively counterbalance each other so that Ca buffering remains constant during beta-adrenergic stimulation, a factor which may be physiologically important. This study also emphasizes the importance of taking into account Ca buffering, particularly in disease states where Ca binding to myofilaments or SERCA may be altered.
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