Functional consequences of detubulation of isolated rat ventricular myocytes Export

@article{citeulike:5196531, abstract = {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 {micro}M) 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 {micro}M) 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. 10.1016/j.cardiores.2004.02.008}, author = {Fowler, Mark R. and Dobson, Rebekah S. and Orchard, Clive H. and Harrison, Simon M.}, citeulike-article-id = {5196531}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cardiores.2004.02.008}, citeulike-linkout-1 = {http://cardiovascres.oxfordjournals.org/cgi/content/abstract/62/3/529}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15158145}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15158145}, day = {1}, doi = {10.1016/j.cardiores.2004.02.008}, journal = {Cardiovasc Res}, keywords = {cardiac, detubulation, myocyte, rat, ventricle}, month = {June}, number = {3}, pages = {529--537}, posted-at = {2009-07-18 05:17:39}, priority = {2}, title = {Functional consequences of detubulation of isolated rat ventricular myocytes}, url = {http://dx.doi.org/10.1016/j.cardiores.2004.02.008}, volume = {62}, year = {2004} }

TY - JOUR ID - citeulike:5196531 L3 - citeulike-article-id:5196531 N2 - 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 {micro}M) 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 {micro}M) 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. 10.1016/j.cardiores.2004.02.008 IS - 3 JF - Cardiovasc Res EP - 537 TI - Functional consequences of detubulation of isolated rat ventricular myocytes VL - 62 SP - 529 KW - cardiac KW - detubulation KW - myocyte KW - rat KW - ventricle AU - Fowler, Mark AU - Dobson, Rebekah AU - Orchard, Clive AU - Harrison, Simon PY - 2004/06/01/ UR - http://dx.doi.org/10.1016/j.cardiores.2004.02.008 ER -