The cardiac persistent sodium current: an appealing therapeutic target?
| dc.contributor.author | Saint, D. | |
| dc.date.issued | 2008 | |
| dc.description | © 2008 British Pharmacological Society | |
| dc.description.abstract | The sodium current in the heart is not a single current with a mono-exponential decay but rather a mixture of currents with different kinetics. It is not clear whether these arise from distinct populations of channels, or from modulation of a single population. A very slowly inactivating component, [INa(P)] INa(P) is usually about 1% of the size of the peak transient current [INa(T)], but is enhanced by hypoxia. It contributes to Na+ loading and cellular damage in ischaemia and re-perfusion, and perhaps to ischaemic arrhythmias. Class I antiarrhythmic agents such as flecainide, lidocaine and mexiletine generally block INA(P) more potently than block of INa(T) and have been used clinically to treat LQT3 syndrome, which arises because mutations in SCN5A produce defective inactivation of the cardiac sodium channel. The same approach may be useful in some pathological situations, such as ischaemic arrhythmias or diastolic dysfunction, and newer agents are being developed with this goal. For example, ranolazine blocks INa(P) about 10 times more potently than INa(T) and has shown promise in the treatment of angina. Alternatively, the combination of INa(P) block with K+ channel block may provide protection from the induction of Torsades de Pointe when these agents are used to treat atrial arrhythmias (eg Vernakalant). In all of these scenarios, an understanding of the role of INa(P) in cardiac pathophysiology, the mechanisms by which it may affect cardiac electrophysiology and the potential side effects of blocking INa(P) in the heart and elsewhere will become increasingly important. | |
| dc.identifier.citation | British Journal of Pharmacology, 2008; 153(6):1133-1142 | |
| dc.identifier.doi | 10.1038/sj.bjp.0707492 | |
| dc.identifier.issn | 0007-1188 | |
| dc.identifier.issn | 1476-5381 | |
| dc.identifier.uri | http://hdl.handle.net/2440/46618 | |
| dc.language.iso | en | |
| dc.publisher | Nature Publishing Group | |
| dc.source.uri | https://doi.org/10.1038/sj.bjp.0707492 | |
| dc.subject | persistent sodium current | |
| dc.subject | cardiac ischaemia | |
| dc.subject | arrhythmias | |
| dc.subject | cardiac electrophysiology | |
| dc.subject | ion channels | |
| dc.title | The cardiac persistent sodium current: an appealing therapeutic target? | |
| dc.type | Journal article | |
| pubs.publication-status | Published |