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Marquis and Sack show that the use-dependent inhibition of Kv2.1 by RY785 is consistent with gated access to a cavity within the channel that traps RY785. While voltage activation is required for access to the blocking site, channel opening itself is not required for access.

Benndorf et al. present a strategy to analyze the functionality of heteromeric ligand-gated ion channels by combining subunit concatenation, mutagenesis, and extensive global fit strategies with intimately coupled Markov models.

Review

Phosphoinositides, rare membrane lipids, mediate powerful second messenger signals to ion channels, endocytosis, and exocytosis, and specify organelle identity. Jensen et al. summarize 20 yr of biophysical research whose key message is that pools of phosphoinositides turn over remarkably quickly to regulate rapid physiological responses.

Research News

Voltage activation, but not channel opening, is required for RY785 to access the central cavity of Kv2 channels, where it promotes voltage sensor deactivation to trap itself in place.

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