BJP: Volatile anesthetic sifluoride and heptafluorane to the human voltage gated Kv1.5 channel open blocking effect.

Background and purpose: Volatile anesthetics have been shown to have different regulatory effects on the voltage-gated potassium channel (Kv1) associated with mammalian vibration.
the molecular and cellular mechanisms of the study to explore the regulatory action of difluorothane or heptafluorane in human Kv1.5 (hKv1.5) channel.
experimental method: Using fixed-point mutation technology to construct 13 single-point mutations in the hole domain of hKv1.5 channel.
use of whole-cell diaphragm pliers to observe the effects of geofluorane and heptafluorane on wild and mutant hKv1.5 channels for heterogeneous expression.
computer simulations predicted the main results of the docking state of terfluorane or heptafluorane in the hKv1.5 channel: difluorothane and heptafluorane both increased hKv1.5 current in mild depolarization, while the hKv1.5 current was reduced when strong depolarization, indicating that the two anesthetics had both stimulating and inhibiting effects on hKv1.5 channels. the inhibition of hKv1.5 channels by
or heptafluorane is mainly due to the blocking effect of the opening of hKv1.5.
Compared with wild channels, the inhibition of difluoraneorane or heptafluorane on hKv1.5 channels was significantly reduced in T480A, V505A and I508A mutant channels.
computational docking simulations found that difluorolanee or heptafluorane was present in the channel cavity and in contact with Thr479, Thr480, Val505 and Ile508.
conclusions and significance: Difluorane and heptafluorane have a blocking effect on the opening of the hKv1.5 channel by interacting with the functionality of specific amino acids in the channel bore.
, therefore, this study clarifies the new molecular basis for the inhibitory regulation of the hKv1.5 channel mediated by difluorothane and heptafluorane.
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