Abstract

The voltage-activated sodium channel Nav1.9 is preferentially expressed in DRG neurons where it is believed to play an important role in pain perception. However, progress in revealing the gating characteristics and pharmacological sensitivities of Nav1.9 has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here we use a protein engineering approach to study the contributions of the four Nav1.9 voltage sensors to channel function. We define individual S3b-S4 paddle motifs within each voltage sensor and show that these structural motifs sense changes in membrane voltage and determine the kinetics of voltage sensor activation.

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