Hypoxia and persistent sodium current

• Published in: European biophysics journal 2002-09, Vol.31 (5), p.323-330
• Main Authors: Hammarström, Anna K M, Gage, Peter W
• Format: Article
• Language: English
• Subjects: Biophysics; Cellular biology; Enzymes; Humans; Hypoxia; Hypoxia - physiopathology; Hypoxia-Ischemia, Brain - physiopathology; Inactivation; Ion Channel Gating; Membrane Potentials; Myocardial Ischemia - physiopathology; Nitric Oxide - pharmacology; Oxygen - metabolism; Pharmacology; Sodium; Sodium - metabolism; Sodium Channels; Sodium Cyanide - pharmacology
• ISSN: 0175-7571; 1432-1017
• DOI: 10.1007/s00249-002-0218-2

During prolonged depolarization of excitable cells, some voltage-activated, tetrodotoxin-sensitive sodium channels are resistant to inactivation and can continue to open for long periods of time, generating a "persistent" sodium current ( I(NaP)). The amplitude of I(NaP) is small [generally less than 1% of the peak amplitude of the transient sodium current ( I(NaT))], activates at potentials close to the resting membrane potential, and is more sensitive to Na channel blocking drugs than I(NaT). It is thought that persistent Na channels are generated by a change in gating of transient Na channels, possibly because of a change in phosphorylation or protein structure, e.g. loss of the inactivation gate. Drugs that block Na channels can prevent the increase in [Ca(2+)](i) in cardiac cells during hypoxia. Hypoxia increases the amplitude of I(NaP). Paradoxically, NO causes a similar increase in I(NaP) and the effects of both can be inhibited by reducing agents such as dithiothreitol and reduced glutathione. It is proposed that an increased inflow of Na(+) during hypoxia increases [Na(+)](i), which in turn reverses the Na/Ca exchanger so that [Ca(2+)](i) rises. An increase in I(NaP) and [Ca(2+)](i) could cause arrhythmias and irreversible cell damage.