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Redox reaction modulates transient and persistent sodium current during hypoxia in guinea pig ventricular myocytes

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Abstract

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 (APD90) of ventricular papillary cells simultaneously, while 1 mmol/GSH could reverse the decreased APA and the shortened APD90 at the same time; 1 mmol/l GSSG strengthened the decrease of APA induced by hypoxia and attenuated the decurtation of APD90 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.

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Acknowledgement

This work was supported by the National Natural Science Foundation of China (No. 30670764) and the Key Scientific Research Program of Educational Bureau of Hubei Province (No. Z200511002).

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Correspondence to Jihua Ma.

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Wang, W., Ma, J., Zhang, P. et al. Redox reaction modulates transient and persistent sodium current during hypoxia in guinea pig ventricular myocytes. Pflugers Arch - Eur J Physiol 454, 461–475 (2007). https://doi.org/10.1007/s00424-007-0219-1

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