- 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.
- 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.
- 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.
- The mechanism of SR Ca2+ leak in CPVT
The K4750Q mutation in ryanodine receptor 2 causes severe catecholaminergic polymorphic ventricular tachycardia. Uehara et al. reveal extensive Ca2+ leak through this mutant receptor and show it is caused by altered gating kinetics, increased Ca2+ sensitivity, and the absence of Ca2+-dependent inactivation.