Intravenous anesthetics have differential effects on human potassium channels.
Ying Tao, Kejie Yao, Jing Wu, Tian Xu, Junhui Lin, Yi Qin, Diansan Su, Shiqing Cai, Weifeng Yu, Xuemei Chen
Acta biochimica et biophysica Sinica September 13, 2024 DOI: 10.3724/abbs.2024151 via PubMed
Summary
AI-generated from the abstractPropofol and ketamine increase the activity of certain potassium channels (TASK-3 and SK3, respectively), while pentobarbital and ketamine decrease the activity of SK1 channels. These effects were observed in Xenopus oocytes expressing seven types of potassium channels. Molecular docking simulations identified specific amino acid residues where each anesthetic binds: propofol to Q126 of TASK-3, ketamine to S290 of SK1 and S467 of SK3, and pentobarbital to S330 and T358 of SK1. Because these potassium channels help regulate respiration, heart rhythm, and blood vessel dilation, the findings suggest a molecular basis for the cardiovascular and respiratory side effects of intravenous general anesthetics.
Study at a glance
| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Xenopus oocytes expressing human potassium channels |
| Interventions | Propofol Pentobarbital Ketamine |
| Keywords | Hypotension Molecular docking Potassium channels Respiratory depression Anesthesia general anesthetics |
| Key finding | Propofol potentiates TASK-3 current, ketamine potentiates SK3 current, and both pentobarbital and ketamine inhibit SK1 current, with specific hydrogen bond interactions identified at key residues. |
Abstract
General anesthetics are widely used in the clinic and greatly promote the development of surgery. However, the incidence of cardiovascular and respiratory complications caused by general anesthetics is still high, and the underlying mechanisms remain incompletely understood. Potassium channels are widely expressed in the heart and blood vessels and participate in regulating blood pressure, heart rate, and other physiological parameters. Whether they are directly affected by intravenous general anesthetics is unclear. Here, we independently express four classes of potassium channels, TASK-1, TASK-3, Kv1.5, Kv2.1, Kir2.1, SK1 and SK3, in Xenopus oocytes. The effects of propofol, pentobarbital and ketamine on these channels are evaluated by their current change. We find that propofol and ketamine potentiate TASK-3 and SK3 current respectively, while pentobarbital and ketamine inhibit SK1 current. To identify the key residues in TASK-3, SK1 and SK3 that interact with intravenous anesthetics, we predict homology models of the three channels and perform molecular docking simulations. The results show that propofol forms a hydrogen bond with Q126 of TASK-3, ketamine forms a hydrogen bond with S290 of SK1 and S467 of SK3, while pentobarbital forms hydrogen bonds with S330 and T358 of SK1. As these potassium channels are closely related to respiratory system regulation, cardiac rhythm and vasodilation, our study provides a new perspective for further study on the mechanism of general anesthetics-induced respiratory and circulatory side effects.