The authors use a fluorescent genetically encoded Ca2+ indicator, GCaMP6f, fused to Orai1 to visualize Ca2+ influx through store-operated Orai1 channels. Combined with whole-cell recording of transfected human cells, this reporter reveals heterogeneity of channel activation and kinetics in STIM1-Orai1 puncta within the same cell.
Neumaier et al. reveal that Zn2+ effects on Cav2.3 channels are complex, can be either inhibitory or stimulatory, and may persist for several minutes after cessation of the Zn2+ signal. A Markov model is developed that can account for Cav2.3 channel currents in the absence and presence of physiological Zn2+ concentrations.
E1784K, the most common Brugada syndrome and long-QT syndrome type 3 mutant, disrupts sodium channel inactivation through two separate mechanisms
Inheritable and de novo variants of voltage-gated sodium channels that lead to sudden cardiac death can affect several different aspects of channel function, making pharmaceutical treatment difficult. Peters et al. show that the E1784K mutant in Nav1.5 alters channel function through two distinct and separable mechanisms.
Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons
The gating of neuronal HCN channels is modulated by the competitive binding of cAMP and TRIP8b, a brain-specific protein that also controls channel trafficking. Porro et al. identify a rational mutation in HCN channels that affects binding of TRIP8b, without altering cAMP affinity or TRIP8b-dependent trafficking. The mutation represents a valuable tool to investigate HCN channels in vivo.