Syncytial basis for diversity in spike shapes and their propagation in detrusor smooth muscle

Syncytial tissues, such as the smooth muscle of the urinary bladder wall, are known to produce action potentials (spikes) with marked differences in their shapes and sizes. The need for this diversity is currently unknown, and neither is their origin understood. The small size of the cells, their syncytial arrangement, and the complex nature of innervation poses significant challenges for the experimental investigation of such tissues. To obtain better insight, we present here a three-dimensional electrical model of smooth muscle syncytium, developed using the compartmental modeling technique, with each cell possessing active channel mechanisms capable of producing an action potential. This enables investigation of the syncytial effect on action potential shapes and their propagation. We show how a single spike shape could undergo modulation, resulting in diverse shapes, owing to the syncytial nature of the tissue. Differences in the action potential features could impact their capacity to propagate through a syncytium. This is illustrated through comparison of two distinct action potential mechanisms. A better understanding of the origin of the various spike shapes would have significant implications in pathology, assisting in evaluating the underlying cause and directing their treatment

Modeling extracellular fields for a three-dimensional network of cells using NEURON

Background: Computational modeling of biological cells usually ignores their extracellular fields, assuming them to be inconsequential. Though such an assumption might be justified in certain cases, it is debatable for networks of tightly packed cells, such as in the central nervous system and the syncytial tissues of cardiac and smooth muscle. New method: In the present work, we demonstrate a technique to couple the extracellular fields of individual cells within the NEURON simulation environment. The existing features of the simulator are extended by explicitly defining current balance equations, resulting in the coupling of the extracellular fields of adjacent cells. Results: With this technique, we achieved continuity of extracellular space for a network model, thereby allowing the exploration of extracellular interactions computationally. Using a three-dimensional network model, passive and active electrical properties were evaluated under varying levels of extracellular volumes. Simultaneous intracellular and extracellular recordings for synaptic and action potentials were analyzed, and the potential of ephaptic transmission towards functional coupling of cells was explored. Comparison with existing method(s): We have implemented a true bi-domain representation of a network of cells, with the extracellular domain being continuous throughout the entire model. This has hitherto not been achieved using NEURON, or other compartmental modeling platforms. Conclusions: We have demonstrated the coupling of the extracellular field of every cell in a threedimensional model to obtain a continuous uniform extracellulat" space. This technique provides a framework for the investigation of interactions in tightly packed networks of cells via their extracellular fields. (C) 2017 Elsevier B.V. All rights reserved

Neurotransmission by ATP: New insights, novel mechanisms

137-147Purines have long been known for their roles in extracellular signaling. One of the most interesting functions to come to light recently has been the involvement, particularly of adenosine 5'-triphosphate (ATP), as a neurotransmitter in the central and the sympathetic nervous system. ATP is stored in and released from synaptic nerve terminals, like other neurotransmitters, and is known to act post-synaptically via specific rapidly-conducting, ligand-gated ion channels, the P2X receptors. Another interesting feature is the discovery that ATP is widely found to be a "co-transmitter" at the same synapses in combination with other neurotransmitters such as noradrenaline, acetylcholine, and GABA, altering our picture of the biophysics and biochemistry of neurotransmission at these synapses. We describe here these and other aspects of neurotransmission by ATP being investigated vigorously today, including recent findings on P2X receptors and those on the synaptic inactivation of ATP by ecto-ATPase. We conclude by pointing out possible pharmacological and clinical implications of neurotransmission by ATP