Effects of the venom of the spider Ornithoctonus hainana on neonatal rat ventricular myocytes cellular and ionic electrophysiology

摘要

Cardiac ion channels are membrane-spanning proteins that allow the passive movement of ions across the cell membrane along its electrochemical gradient, which regulates the resting membrane potential as well as the shape and duration of the cardiac action potential. Additionally, they have been recognized as potential targets for the actions of neurotransmitters, hormones and drugs of cardiac diseases. Spider venoms contain high abundant of toxins that target diverse ion channels and have been considered as a potential resource of new constituents with specific pharmacological properties. However, few peptides from spider venoms were detected as cardiac channel antagonists. In order to explore the effects of the venom of Ornithoctonus hainana on the action potential and ionic currents of neonatal rat ventricular myocytes (NRVMs), whole cell patch clamp technique was used to record action potential duration (APD), sodium current (I-Na), L calcium current (I-CaL), rapidly activating and inactivating transient outward currents (I-to1), rapid (I-Kr) and slow (I-Ks) components of the delayed rectifier currents and the inward rectifier currents (I-K1). Our results showed that 100 mu g/mL venom obviously prolonged APDs. Significantly, the venom could inhibit I-Na and I-CaL. effectively, while no evident inhibitory effects on cardiac K+ channels (I-to1, I-ks, I-kr and I-k1) were observed, suggesting that the venom represented a multifaceted pharmacological profile. The effect of venom on Na+ and Ca2+ currents of ventricular myocytes revealed that the hainan venom as a rich resource of cardiac channel antagonists might be valuable tools for the investigation of both channels and drug development. (C) 2014 Elsevier Ltd. All rights reserved.