- VSD regulation of NaV inactivation
Hsu et al. probe voltage-gated Na+ channels that are inactivation deficient with voltage-clamp fluorometry. They find that in the time domain of an action potential, the voltage-sensing domain (VSD) of domain IV regulates fast inactivation onset while the domain III VSD determines its recovery.
- Doublet stimulation increases on Ca2+ and force
High-frequency paired stimuli used to initiate a tetanus result in increased force and rate of force development in skeletal muscle. Bakker et al. investigate this mechanism and find that doublet stimulation increases the amount of Ca2+ bound to troponin C, resulting in rapid force development.
- Voltage-gate coupling in truncated BK channels
Both cellular depolarization and intracellular Ca2+ can gate open large conductance Ca2+-activated K+ channels. Zhang et al. show that the intracellular gating ring, which forms the Ca2+-sensing machinery of the channel, is also required for activated voltage sensors to effectively gate open the pore.
- Phasic and tonic response mechanisms in RGCs
Visual stimuli of different frequencies are encoded in the retina using transient and sustained responses. Zhao et al. describe the different strategies that are used by four types of retinal ganglion cells to shape photoresponse kinetics.
- Intrinsically liganded CNBhD in KCNH activation
hEAG1 is a member of the KCNH family of ion channels, which are characterized by C-terminal regions with homology to cyclic nucleotide–binding domains (CNBhDs). Zhao et al. show that an “intrinsic ligand” occupying the CNBhD binding pocket promotes the activated and open state of the channel.
- ADPR binding on TRPM2
ADP ribose (ADPR) is an endogenous ligand for the transient receptor potential melastatin 2 (TRPM2) channel. Yu et al. identify 11 residues in the NUDT9 homology domain of TRPM2 that form a binding site for ADPR involving van der Waals, polar solvation, and electronic interactions.
- CaM regulates Na+ channel persistent current
The molecular mechanisms controlling “persistent” current through voltage-gated Na+ channels are poorly understood. Yan et al. show that apocalmodulin binding to the intracellular C-terminal domain limits persistent Na+ flux and accelerates inactivation across the voltage-gated Na+ channel family.