Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload.
Late sodium current in cardiac cells is very small compared with the fast component, but as it flows throughout the action potential it may make a substantial contribution to sodium loading during each cardiac cycle. Late sodium current may contribute to triggering arrhythmia in two ways: by causing repolarisation failure (early after depolarisations); and by triggering late after depolarisations attributable to calcium oscillations in sodium-calcium overload conditions. Reduction of late sodium current would therefore be expected to have therapeutic benefits, particularly in disease states such as ischaemia in which sodium-calcium overload is a major feature.
Noble
D
D
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK. denis.noble@physiol.ox.ac.uk
Noble
P J
PJ
D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013779:Tetrodotoxin / Q000502:physiology
D015220:Calcium Channels; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin; D012964:Sodium; D002118:Calcium