Na+ channel modulation and force-frequency relationship in human myocardium
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- 作者：Jochen Müller-Ehmsen ; Klara Brixius ; Costas Schulze and R. H. G. Schwinger
- 关键词：Key words Force ; frequency relationship ; Human myocardium ; Lidocaine ; BDF 9148 ; Sodium homeostasis ; Na+ channel modulator
- 刊名：Naunyn-Schmiedeberg's Archives of Pharmacology
- 出版年：1997
- 出版时间：May 1997
- 年：1997
- 卷：355
- 期：6
- 页码：727-732
- 全文大小：219 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Pharmacology and Toxicology
Neurosciences - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1912
文摘
The enhancement of force of contraction (FOC) following increasing frequencies of stimulation is an important mechanism of positive inotropy in human myocardium. The present study aimed to investigate the influence of alterations in Na+ influx on FFR in human myocardium. Isometric FOC of electrically stimulated right auricular trabeculae (AUT, n=12) from human nonfailing hearts (n=8) was measured at different stimulation rates (0.5-3 Hz) under control conditions, after increasing Na+ influx by the addition of (±)BDF 9148 (BDF, 3 μmol l-1) and after decreasing Na+ influx by the addition of lidocaine (LIDO, 10 μmol l-1). Additionally, the rate dependent changes in diastolic tension (DT) were measured in all experiments. Under control conditions FOC increased with increasing frequencies of stimulation. The rate at which maximal FOC was observed (SFmax) was 2.0±0.2 Hz and maximal increase in FOC (PIEmax) by increasing frequency of stimulation was +1.5±0.5 mN. After increase of Na+ influx by BDF (3 μmol l-1) SFmax was decreased to 0.8±0.1 Hz (p<0.05 versus control) and PIEmax was +0.1±0.3 mN (p<0.05). When Na+ influx was diminished by LIDO (10 μmol l-1) SFmax and PIEmax were increased compared to control (2.4±0.1 Hz and +4.1±0.9 mN, p<0.05 versus control). The diastolic tension (DT) of AUT at 3 Hz was not changed at higher rates in the control group and after application of LIDO (10 μmol l-1), whereas after enhancement of Na+ influx by BDF there was an increase in DT of +0.7±0.2 at 3Hz (p<0.05 versus control and LIDO). An enhanced Na+ influx leads to a decrease in the optimal frequency and to a smaller force potentiation by higher stimulation rates which could be at least partly due to incomplete relaxation at higher frequencies, whereas a reduced Na+ influx is followed by opposite alterations. It is concluded that besides Ca2+ handling also Na+ influx and Na+ homeostasis might determine the frequency-induced force potentiation in human myocardium. Thus, the negative FFR in diseased human myocardium might result from changes in cellular Ca2+ or Na+ regulatory sites.