Importantly bioelectric circuits in tissues Fig A

(4) Importantly, bioelectric circuits in tissues (Fig. 2A) have a capacity to store long-term patterning information. An example is planarian anterior-posterior patterning: during regeneration, each fragment cut from a worm needs to build a head and tail at their correct ends. This process is regulated by a bioelectric circuit, evidence for which was first discovered decades ago [82,83]. Brief exposure to gap junction blocker or H,K-ATPase inhibitors alter the endogenous bioelectric distribution and cause the fragment to make two-head or no-head pieces respectively [[84], [85], [86]] (Fig. 2B and C). Remarkably, the two-headed fragments continue to regenerate two heads when pieces are cut and allowed to regenerate in plain water (Fig. 2D) [86]. The permanent conversion of this animal's target morphology to a two-headed bipolar form occurs via a transient stimulus, without genomic editing [86], but can be re-set back to normal for future rounds of regeneration by the drug SCH28080 [87]. A recent study identified yet another possible permanent state for planaria, that of a stochastically-destabilized form which is anatomically and histologically indistinguishable from wild-type but that bears an overall depolarized state that causes fragments to sometimes regenerate one and sometimes two heads (in a fixed proportion) [87]. These data reveal that the body specified by a wild-type genomic sequence can store one of several bioelectric memories that, when activated, drive distinct anatomical outcomes [7,88]. In the above experimental examples, changes of bioelectric signals such as the local electric potential occurring at the multicellular scale can result in spatio-temporal patterns that trigger downstream biochemical processes, e.g., via second-messenger cascades such as serotonin. These processes are conserved across different bioelectric contexts, including L-R patterning, cancer, and guidance of innervation. [6]. The crucial fact is that the map of electric potentials can influence the spatio-temporal distribution of signaling Roflumilast (e.g., serotonin and butyrate) and ions (e.g., calcium) over multicellular ensembles [6,7,9,31,54,89]. Also, the transference of biological macromolecules (e.g., small non-coding RNAs such as microRNA) affecting gene expression and ion channel translation could allow some control of bioelectric states over small cell domains [36,90]. We believe that animal models and theoretical simulations integrating biochemical and bioelectric networks may then suggest new opportunities for patterned control of growth. Avoiding clinical risks will be an important aspect of biomedical applications in this field: bioelectricity and ion channels regulate multiple functions in the body (e.g., the cardiac rhythm) and are also involved in other cell characteristics (e.g., adhesion, volume regulation, and apoptosis) that are crucial to many biological processes. Thus, in order to exploit the large body of (already human-approved and novel) ion channel drugs as electroceuticals for injury and disease, extensive predictive modeling platforms will need to be developed that can help design protocols with tightly-circumscribed effects on the bioelectric state of multicellular domains of specific tissues [55,[91], [92], [93]]. The development of these platforms can be assisted by the biophysical understanding of the origin and evolution of electric potential patterns in vivo [6,13,[30], [31], [32], [33], [34],37,38,94].
Bioelectric model equations
Results and discussion
Conclusions Theoretical approaches to cortical patterns have invoked neuron potentials and gap-junction connectivities for the description of emerging large-scale Turing structures [133]. Recent experimental evidence suggests that bioelectric coupling between non-neural cells also establishes essential links between single-cell processes and large-scale multicellular phenomena [6,7,31,89,100]. Indeed, when cells are coupled together, their individual properties can be influenced by the electrical characteristics of the whole ensemble. Although synthetic approaches have been successful in creating electrically excitable tissues which support bioelectric dynamics in vitro [101], the processes that allow intercellular information transfer are not known at the same level of detail as the basic genetic mechanisms.