Sodium channel blockade reduces hypoxic sodium loading and sodium-dependent calcium loading

Area of Science:

• Cardiology
• Cell Physiology
• Biophysics

Background:

• Hypoxic myocardium experiences increased intracellular calcium ([Ca2+]i), driven by elevated intracellular sodium ([Na+]i).
• The precise source of this sodium influx during hypoxia remains unidentified.

Purpose of the Study:

• To investigate the role of voltage-gated sodium channels in hypoxic sodium and calcium loading.
• To assess the impact of sodium channel blockade on reoxygenation-induced hypercontracture in cardiac myocytes.

Main Methods:

• Isolated adult rat cardiac myocytes were loaded with indicators for intracellular sodium (SBFI) and calcium (indo-1).
• Cells were subjected to glucose-free hypoxia and treated with voltage-gated sodium channel inhibitors (R 56865, tetrodotoxin, lidocaine) and a sodium-hydrogen exchange blocker (ethylisopropylamiloride).
• Effects on intracellular ion concentrations and cellular hypercontracture were measured.

Main Results:

• Hypoxic conditions led to significant increases in both intracellular sodium ([Na+]i) and calcium ([Ca2+]i).
• Inhibition of voltage-gated sodium channels with R 56865 and tetrodotoxin markedly reduced hypoxic sodium and calcium loading.
• Sodium channel blockers and ethylisopropylamiloride significantly attenuated reoxygenation-induced hypercontracture.

Conclusions:

• Voltage-gated sodium channels serve as a significant pathway for sodium influx during hypoxia in cardiac myocytes.
• These channels are implicated in sodium-dependent calcium loading and subsequent hypercontracture upon reoxygenation.
• Blocking sodium channels may protect against hypoxic cardiac injury.