Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 channels

TRPA1 is a Ca2+-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca2+, with low Ca2+ potentiating and high Ca2+ inactivating TRPA1. However, it remains unknown how Ca2+ exerts such contrasting effects. Here, we show that Ca2+ regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca2+-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca2+-evoked potentiation of TRPA1 at low Ca2+, but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca2+. Ca2+-dependent potentiation and inactivation of TRPA1 were selectively prevented by disrupting the interaction of the carboxy-lobe of calmodulin with a calmodulin-binding domain in the C-terminus of TRPA1. Calmodulin is thus a critical Ca2+ sensor enabling TRPA1 to respond to diverse Ca2+ signals distinctly

Photobiomodulation devices for hair regrowth and wound healing: a therapy full of promise but a literature full of confusion.

yesPhotobiomodulation is reported to positively influence hair regrowth, wound healing, skin rejuvenation, and psoriasis. Despite rapid translation of this science to commercial therapeutic solutions, significant gaps in our understanding of the underlying processes remain. The aim of this review was to seek greater clarity and rationality specifically for the selection of optical parameters for studies on hair regrowth and wound healing. Our investigation of 90 reports published between 1985-2015 revealed major inconsistencies in optical parameters selected for clinical applications. Moreover, poorly understood photoreceptors expressed in skin such as cytochrome c oxidase, cryptochromes, opsins, may trigger different molecular mechanisms. All this could explain the plethora of reported physiological effects of light. To derive parameters for optimal clinical efficacy of photobiomodulation, we recommend a more rational approach, underpinning clinical studies with research of molecular targets and pathways using well-defined biological model systems enabling easy translation of optical parameters from in vitro to in vivo. Furthermore, special attention needs to be paid when conducting studies for hair regrowth, aiming for double-blind, placebo-controlled randomized clinical trials as the gold standard for quantifying hair growth.European Marie-Curie Actions Programme, Grant agreement no.: 60788

Can cephalopods Vomit? Hypothesis based on a review of circumstantial evidence and preliminary experiemntal observations

In representative species of all vertebrate classes, the oral ejection of upper digestive tract contents by vomiting or regurgitation is used to void food contaminated with toxins or containing indigestible material not voidable in the feces. Vomiting or regurgitation has been reported in a number of invertebrate marine species (Exaiptasia diaphana, Cancer productus, and Pleurobranchaea californica), prompting consideration of whether cephalopods have this capability. This “hypothesis and theory” paper reviews four lines of supporting evidence: (1) the mollusk P. californica sharing some digestive tract morphological and innervation similarities with Octopus vulgaris is able to vomit or regurgitate with the mechanisms well characterized, providing an example of motor program switching; (2) a rationale for vomiting or regurgitation in cephalopods based upon the potential requirement to void indigestible material, which may cause damage and ejection of toxin contaminated food; (3) anecdotal reports (including from the literature) of vomiting- or regurgitation-like behavior in several species of cephalopod (Sepia officinalis, Sepioteuthis sepioidea, O. vulgaris, and Enteroctopus dofleini); and (4) anatomical and physiological studies indicating that ejection of gastric/crop contents via the buccal cavity is a theoretical possibility by retroperistalsis in the upper digestive tract (esophagus, crop, and stomach). We have not identified any publications refuting our hypothesis, so a balanced review is not possible. Overall, the evidence presented is circumstantial, so experiments adapting current methodology (e.g., research community survey, in vitro studies of motility, and analysis of indigestible gut contents and feces) are described to obtain additional evidence to either support or refute our hypothesis. We recognize the possibility that further research may not support the hypothesis; therefore, we consider how cephalopods may protect themselves against ingestion of toxic food by external chemodetection prior to ingestion and digestive gland detoxification post-ingestion. Reviewing the evidence for the hypothesis has identified a number of gaps in knowledge of the anatomy (e.g., the presence of sphincters) and physiology (e.g., the fate of indigestible food residues, pH of digestive secretions, sensory innervation, and digestive gland detoxification mechanisms) of the digestive tract as well as a paucity of recent studies on the role of epithelial chemoreceptors in prey identification and food intakeVersión del edito

Emerging Roles of the Membrane Potential: Action Beyond the Action Potential

Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell’s compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical roles that the RMP has in a variety of cell types beyond the action potential. Whereas most biologists would perceive that the RMP is primarily about excitability, the data show that in fact excitability is only a small part of it. Emerging evidence show that a dynamic membrane potential is critical for many other processes including cell cycle, cell-volume control, proliferation, muscle contraction (even in the absence of an action potential), and wound healing. Modulation of the RMP is therefore a potential target for many new drugs targeting a range of diseases and biological functions from cancer through to wound healing and is likely to be key to the development of successful stem cell therapies