Whole-cell and cell-attached patch clamp techniques were applied on isolated guinea pig ventricular myocytes to study the possible regulatory mechanisms of redox agent on persistent and transient
sodium current related to
hypoxia. The results showed that
hypoxia for 15 min increased persistent
sodium current (I (Na.P)) and decreased transient
sodium current (I (Na.T)) at the same time, while 1 mmol/l of
reduced glutathione (GSH) could reverse the increased I (Na.P) and the decreased I (Na.T) simultaneously. Both persistent and transient
sodium channel activities could be reversed concurrently again by application of 1 mmol/l
oxidized glutathione (
GSSG).
Hypoxia for 15 min decreased the action potential amplitude (APA) and shortened action potential duration at 90% repolarization (APD(90)) of ventricular papillary cells simultaneously, while 1 mmol/GSH could reverse the decreased APA and the shortened APD(90) at the same time; 1 mmol/l
GSSG strengthened the decrease of APA induced by
hypoxia and attenuated the decurtation of APD(90) induced by
hypoxia compared with pure
hypoxia. The correlation between I (Na.P) and I (Na.T) and the effects of GSH and
GSSG on them suggested that during
hypoxia, redox regulation played a tremendous part in
sodium channel activity and that I (Na.P) and I (Na.T) might be charged by the same channel with different gating modes in guinea pig ventricular myocytes. Judging from their alterations during
hypoxia and exposure to GSH and
GSSG, we speculated that an interconversion might exist between I (Na.P) and I (Na.T). That was when one of them was increased, the other was decreased, and vice versa.