© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Functional consequences of detubulation of isolated rat ventricular myocytes
School of Biomedical Sciences, University of Leeds, Worsley Building, Leeds, West Yorkshire, LS2 9NQ, UK
* Corresponding author. Tel.: +44-113-343-4262; fax: +44-113-343-4262. Email address: s.m.harrison{at}leeds.ac.uk
Objective: Recent work has suggested that Na+/Ca2+ exchange (NCX) and L-type Ca2+ current (ICa) are located predominantly in the t-tubules of cardiac ventricular myocytes, which therefore represent a microdomain for the regulation of intracellular Na+ (Nai) and Ca2+ (Cai). The aim of this study was to investigate the role of the t-tubules in the response of Cai and contraction to interventions that alter the transsarcolemmal Na+gradient. Methods: Enzymatically isolated and detubulated Wistar rat ventricular myocytes were investigated using fluorescence microscopy and optical detection of cell length. Results: In unstimulated cells, spontaneous contractile activity increased when extracellular [Na+] was decreased or strophanthidin (100 µM) was added to the bathing solution, but the increase was significantly smaller in detubulated cells than in control cells. In electrically stimulated cells, strophanthidin increased Nai to a similar extent in normal and detubulated cells, although the associated increase in Ca2+ transient amplitude and contraction were significantly smaller in detubulated cells. Similarly, tetrodotoxin (TTX, 10 µM) attenuated the Ca2+ transient and contraction less in detubulated than in control cells. Increasing stimulation rate (0.05–1 Hz) caused little change or a small increase in contraction amplitude in control cells, but a significant decrease in contraction amplitude in detubulated cells, although the change of Nai caused by increasing stimulation rate from 0 to 1 Hz was not significantly different in the two cells types. Conclusion: It is concluded that although some Na/K ATPase, NCX and Na+channel activity is present on the surface membrane, the t-tubules play a major role in the modulation of contraction via NCX, allowing changes of the transsarcolemmal Na+gradient to be translated into changes of Cai.
KEYWORDS Sodium; Calcium; Cardiac muscle; t-tubules; Na/Ca exchanger
Time for primary review 28 days
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