Selective depolarization of transmembrane potential alters muscle patterning and muscle cell localization in Xenopus laevis embryos

Abstract

The correct anatomical placement and precise determination of specific cell types is required for the establishment of normal embryonic patterning. Understanding these processes is also important for progress in regenerative medicine and cancer biology. Transmembrane voltage gradients across embryonic tissues can mediate cellular communication to regulate the processes of proliferation, migration, and differentiation. Our past work showed that selective depolarization of an endogenous instructor cell population in Xenopus laevis in vivo induced a melanoma-like phenotype in the absence of genetic damage. Here, we use a hypersensitive glycine-gated chloride channel (GlyR) under control of tissue-specific promoters to show that instructor cells resident within muscle are more effective at triggering the metastatic conversion of ectodermal melanocytes than those similar cells within the nervous system. Moreover, depolarization of muscle cells results in aberrant muscle patterning and the appearance of cells expressing muscle markers within the neural tube, which impacts but does not abolish the animals' ability to learn in an associative conditioning assay. Taken together, our data reveal new details of long-range (non-cell-autonomous) reprogramming of cell behavior via alteration of the resting potential of specific embryonic subpopulations.

The brain is required for normal muscle and nerve patterning during early Xenopus development

“…Considering the many examples of muscle formation and patterning mediated by bioelectrical signaling in both mammals 30 and amphibians 31 , as well as the ability of some channels to rescue profound embryonic defects 32 , we wondered whether the exogenous expression of a specific ion channel, hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2), could counter the effects of brain removal. The HCN2 channel is known to be an important modulator of functional bioelectric state 33 and can hyperpolarize cells, and it has been recently shown to be implied in firing and rhythmic properties of the cholinergic neurons in both CNS and gastrointestinal tract 34 , 35 .…”

“…NMDA-glutamate receptors (NMDAR) in muscles are also excitatory and depolarize the muscle cells leading to their contraction (such as carbachol does on nAChR). Given recent work on the importance of steady-state developmental voltage gradients during Xenopus muscle patterning 31 , our findings are consistent with the hypothesis that maintaining the balance between developmental bioelectricity (resting potential gradients) and discrete action potentials at NMJ may be important during muscle development and inhibitory signals from the brain (probably via extra-spinal alternative pathways) may be acting to shield the developing muscle cells from such excitatory stimulus that might cause muscle mispatterning (Fig. 7b , brown rectangle representing muscle membrane).…”

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

“…; Wheeler & Liu, ; Pratt & Khakhalin, ). Likewise, these data provide new insights into endogenous physiological regulators of muscle development in vivo (Lobikin, ).…”

Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?

“…[90][91][92][93] Likewise, bioelectric controls of serotonin movement through gap junctions mediate the effect of ion channel drugs on ectopic innervation from transplanted organs [94][95][96] and conversion of cells to a metastatic phenotype. 95,[97][98][99] However, prior work placed SERT downstream of voltage changes, and it was not known that SSRIs could also function upstream to alter V mem of non-neural cells (relevant effects on neurons have been observed however 100,101 ). In this study, we show this in planaria; moreover, the changes are persistent long after the SSRI is withdrawn.…”