Simultaneous measurements of mitochondrial NADH and Ca(2+) during increased work in intact rat heart trabeculae |
| |
Authors: | Brandes Rolf Bers Donald M |
| |
Institution: | Novasite Pharmaceuticals, San Diego, California 92121, USA. rbrandes@alumni.ucsd.edu |
| |
Abstract: | The main goal of this study is to investigate the role of mitochondrial Ca(2+)], Ca(2+)](m), in the possible up-regulation of the NADH production rate during increased workload. Such up-regulation is necessary to support increased flux through the electron transport chain and increased ATP synthesis rates. Intact cardiac trabeculae were loaded with Rhod-2(AM), and Ca(2+)](m) and mitochondrial NADH] (NADH](m)) were simultaneously measured during increased pacing frequency. It was found that 53% of Rhod-2 was localized in mitochondria. Increased pacing frequency caused a fast, followed by a slow rise of the Rhod-2 signal, which could be attributed to an abrupt increase in resting cytosolic Ca(2+)], and a more gradual rise of Ca(2+)](m), respectively. When the pacing frequency was increased from 0.25 to 2 Hz, the slow Rhod-2 component and the NADH signal increased by 18 and 11%, respectively. Based on a new calibration method, the 18% increase of the Rhod-2 signal was calculated to correspond to a 43% increase of Ca(2+)](m). There was also a close temporal relationship between the rise (time constant approximately 25 s) and fall (time constant approximately 65 s) of Ca(2+)](m) and NADH](m) when the pacing frequency was increased and decreased, respectively, suggesting that increased workload and Ca(2+)](c) cause increased Ca(2+)](m) and consequently up-regulation of the NADH production rate. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|