Effects of Na+/Ca2+ exchange induced by SR Ca2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes.

@article{citeulike:1139258, abstract = {In cardiac cells, evoked Ca2+ releases or spontaneous Ca2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na+-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90\% repolarization (APD90) by 50\% and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca2+ exchange inhibitor KB-R7943 (5 microM) or after inhibition of SR Ca2+ release with ryanodine (20 microM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload.}, address = {Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA.}, author = {Spencer, C. I. and Sham, J. S. }, citeulike-article-id = {1139258}, doi = {10.1152/ajpheart.00274.2003}, issn = {0363-6135}, journal = {Am J Physiol Heart Circ Physiol}, keywords = {action, adp, afterdepolarisation, calcium, cardiac, exchanger, guinea, myocyte, ncx, pig, potential, reticulum, sarcoplasmic, sodium, sr, ventricular}, month = {December}, number = {6}, posted-at = {2007-03-04 04:58:03}, priority = {2}, title = {Effects of Na+/Ca2+ exchange induced by SR Ca2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes.}, url = {http://dx.doi.org/10.1152/ajpheart.00274.2003}, volume = {285}, year = {2003} }

TY - JOUR ID - citeulike:1139258 L3 - citeulike-article-id:1139258 TI - Effects of Na+/Ca2+ exchange induced by SR Ca2+ release on action potentials and afterdepolarizations in guinea pig ventricular myocytes. JF - Am J Physiol Heart Circ Physiol VL - 285 IS - 6 AD - Division of Pulmonary and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA. SN - 0363-6135 N2 - In cardiac cells, evoked Ca2+ releases or spontaneous Ca2+ waves activate the inward Na+/Ca2+ exchange current (INaCa), which may modulate membrane excitability and arrhythmogenesis. In this study, we examined changes in membrane potential due to INaCa elicited by sarcoplasmic reticulum (SR) Ca2+ release in guinea pig ventricular myocytes using whole cell current clamp, fluorescence, and confocal microscopy. Inhibition of INaCa by Na+-free, Li+-containing Tyrode solution reversibly abbreviated the action potential duration at 90% repolarization (APD90) by 50% and caused SR Ca2+ overload. APD90 was similarly abbreviated in myocytes exposed to the Na+/Ca2+ exchange inhibitor KB-R7943 (5 microM) or after inhibition of SR Ca2+ release with ryanodine (20 microM). In the absence of extracellular Na+, spontaneous SR Ca2+ releases caused minimal changes in resting membrane potential. After the myocytes were returned to Na+-containing solution, the potentiated intracellular Ca2+ concentration ([Ca2+]i) transients dramatically prolonged APD90 and [Ca2+]i oscillations caused delayed and early afterdepolarizations (DADs and EADs). Laser-flash photolysis of caged Ca2+ mimicked the effects of spontaneous [Ca2+]i oscillations, confirming that APD prolongation, DADs, and EADs could be ascribed to intracellular Ca2+ release. These results suggest that Na+/Ca2+ exchange is a major physiological determinant of APD and that INaCa activation by spontaneous SR Ca2+ release/oscillations, depending on the timing, can account for both DADs and EADs during SR Ca2+ overload. KW - action KW - adp KW - afterdepolarisation KW - calcium KW - cardiac KW - exchanger KW - guinea KW - myocyte KW - ncx KW - pig KW - potential KW - reticulum KW - sarcoplasmic KW - sodium KW - sr KW - ventricular AU - Spencer, CI AU - Sham, JS PY - 2003/12// UR - http://dx.doi.org/10.1152/ajpheart.00274.2003 ER -