Opto-chemogenetic inhibition of L-type Ca1 channels in neurons through a membrane-assisted molecular linkage.

Genetically encoded inhibitors of Ca1 channels that operate via C-terminus-mediated inhibition (CMI) have been actively pursued. Here, we advance the design of CMI peptides by proposing a membrane-anchoring tag that is sufficient to link the inhibitory modules to the target channel as well as chemical and optogenetic modes of system control. We designed and implemented the constitutive and inducible CMI modules with appropriate dynamic ranges for the short and long variants of Ca1.

A Non-Invasive and DNA-free Approach to Upregulate Mammalian Voltage-Gated Calcium Channels and Neuronal Calcium Signaling via Terahertz Stimulation.

Mammalian voltage-gated calcium channels (Ca) play critical roles in cardiac excitability, synaptic transmission, and gene transcription. Dysfunctions in Ca are implicated in a variety of cardiac and neurodevelopmental disorders. Current pharmacological approaches to enhance Ca activity are limited by off-target effects, drug metabolism issues, cytotoxicity, and imprecise modulation.

Chronic Ca imaging of cortical neurons with long-term expression of GCaMP-X.

Dynamic Ca signals reflect acute changes in membrane excitability, and also mediate signaling cascades in chronic processes. In both cases, chronic Ca imaging is often desired, but challenged by the cytotoxicity intrinsic to calmodulin (CaM)-based GCaMP, a series of genetically-encoded Ca indicators that have been widely applied. Here, we demonstrate the performance of GCaMP-X in chronic Ca imaging of cortical neurons, where GCaMP-X by design is to eliminate the unwanted interactions between the conventional GCaMP and endogenous (apo)CaM-binding proteins.

Cytosolic peptides encoding Ca1 C-termini downregulate the calcium channel activity-neuritogenesis coupling.

L-type Ca (Ca1) channels transduce channel activities into nuclear signals critical to neuritogenesis. Also, standalone peptides encoded by Ca1 DCT (distal carboxyl-terminus) act as nuclear transcription factors reportedly promoting neuritogenesis. Here, by focusing on exemplary Ca1.