Homocysteine modulates sodium channel currents in human atrial myocytes.

Hyperhomocysteinemia has been proposed as an important risk factor for cardiac arrhythmias and ischemia worldwide. However, the cellular mechanism underlying toxic effects of homocysteine on hearts remains conjectural. It is well known that aberrant sodium channels can promote the development of cardiac arrhythmias and ischemic injury. So the present study was to investigate toxic effects of homocysteine on sodium currents recorded in human atrial cells. Human atrial myocytes were acutely enzymatically isolated and the whole-cell patch clamp technique was employed to record sodium currents and membrane potential in human atrial cells in the absence and presence of homocysteine. We found that in human atrial myocytes, sodium currents were significantly increased by pathological concentration of homocysteine with the maximum activation potential shifted toward the positive potential. However, physiological concentration of homocysteine did not have any effects on sodium currents. The time constants for time-dependent activation (tau(act)) and inactivation (tau(inact)) of sodium currents were both markedly shortened by elevated homocysteine levels. The further channel kinetic data showed that elevated homocysteine levels shifted the inactivation curve towards positive potential and accelerated the recovery from inactivation of sodium channel, but did not affect the activation of sodium channel. Additionally, the resting membrane potential of human atrial myocytes was obviously depolarized by elevated homocysteine levels in the current clamp model. Taken together, the data presented in this study first revealed that increased homocysteine levels caused the abnormality of sodium currents in human atrial cells by slowing the inactivation and promote the recovery of sodium channels, which provides a better understanding of hyperhomocysteinemia associated cardiac arrhythmias and ischemia.