Most animals can distinguish two distinct types of touch stimuli: gentle (innocuous) and harsh (noxious/painful) touch, however, the underlying mechanisms are not well understood. Caenorhabditis elegans is a useful model for the study of gentle touch sensation. However, little is known about harsh touch sensation in this organism. Here we characterize harsh touch sensation in C. elegans. We show that C. elegans exhibits differential behavioural responses to harsh touch and gentle touch. Laser ablations identify distinct sets of sensory neurons and interneurons required for harsh touch sensation at different body segments. Optogenetic stimulation of the circuitry can drive behaviour. Patch-clamp recordings reveal that TRP family and amiloride-sensitive Na⁺ channels mediate touch-evoked currents in different sensory neurons. Our work identifies the neural circuits and characterizes the sensory channels mediating harsh touch sensation in C. elegans, establishing it as a genetic model for studying this sensory modality.

Significance: By harnessing the unique interactions between infrared fluorescent protein and its chromophore, we have designed an infrared fluorogenic protease reporter (iProtease). A fluorogenic protease reporter is ideal for imaging protease activity in vivo, whereas a FRET-based reporter is limited by poor signal and requirement of image processing. The iProtease scaffold may be used as a core module to design reporters of various proteases with specific activity. This technology will aide important applications, including monitoring protease activity in vivo, dissecting signaling pathways that regulate protease activity, and high-throughput screening of protease inhibitors for drug development and biological study. Our work shows that phytochrome-derived infrared fluorescent protein is a promising scaffold in engineering fluorogenic reporters for visualizing spatiotemporal dynamics of cell signaling in vivo .

Ion channels provide the basis for the nervous system’s intrinsic electrical activity. Neuronal excitability is a characteristic property of neurons and is critical for all functions of the nervous system. Glia cells fulfill essential supportive roles, but unlike neurons, they also retain the ability to divide. This can lead to uncontrolled growth and the formation of gliomas. Ion channels are involved in the unique biology of gliomas pertaining to peritumoral pathology and seizures, diffuse invasion, and treatment resistance. The emerging picture shows ion channels in the brain at the crossroads of neurophysiology and fundamental pathophysiological processes of specific cancer behaviors as reflected by uncontrolled proliferation, infiltration, resistance to apoptosis, metabolism, and angiogenesis. Ion channels are highly druggable, making them an enticing therapeutic target. Targeting ion channels in difficult-to-treat brain tumors such as gliomas requires an understanding of their extremely heterogenous tumor microenvironment and highly diverse molecular profiles, both representing major causes of recurrence and treatment resistance. In this review, we survey the current knowledge on ion channels with oncogenic behavior within the heterogeneous group of gliomas, review ion channel gene expression as genomic biomarkers for glioma prognosis and provide an update on therapeutic perspectives for repurposed and novel ion channel inhibitors and electrotherapy.

Proliferating cells, typically considered “nonexcitable,” nevertheless, exhibit regulation by bioelectric signals. Notably, voltage-gated sodium channels (VGSC) that are crucial for neuronal excitability are also found in progenitors and up-regulated in cancer. Here, we identify a role for VGSC in proliferation of Drosophila neuroblast (NB) lineages within the central nervous system. Loss of paralytic (para), the sole gene that encodes Drosophila VGSC, reduces neuroblast progeny cell number. The type II neuroblast lineages, featuring a population of transit-amplifying intermediate neural progenitors (INP) similar to that found in the developing human cortex, are particularly sensitive to para manipulation. Following a series of asymmetric divisions, INPs normally exit the cell cycle through a final symmetric division. Our data suggests that loss of Para induces apoptosis in this population, whereas overexpression leads to an increase in INPs and overall neuroblast progeny cell numbers. These effects are cell autonomous and depend on Para channel activity. Reduction of Para expression not only affects normal NB development, but also strongly suppresses brain tumor mass, implicating a role for Para in cancer progression. To our knowledge, our studies are the first to identify a role for VGSC in neural progenitor proliferation. Elucidating the contribution of VGSC in proliferation will advance our understanding of bioelectric signaling within development and disease states.