Neuronal Function
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
A typical neuron has a cell body (or soma) with fibre-like processes called dendrites and axons emerging from it. The dendrites are branches that leave the cell body and receive information from adjoining neurons. When a neuron is activated, an electrical impulse called an action potential is generated at the axon hillock and then conducted along the axon. Electrical synapses are formed by gap junctions that form low-resistance channels between the presynaptic and postsynaptic elements so that various ions can freely move between the two related neurons and mediate rapid transfer of signals that can spread through large pools of neurons. They may be found at dendrodendritic sites of contact between nerves that synchronize neuronal activity, but they are uncommon in the mammalian nervous system. In general, ligand-gated channels that allow sodium to enter the postsynaptic neuron are excitatory, whereas channels that allow chloride to enter (or potassium to exit) are inhibitory.
Muscle and Nerve Histology
Maher Kurdi in Neuromuscular Pathology Made Easy, 2021
This chapter discusses the basic principles of muscle histology, which will help in understanding the pathogenetic mechanism of most neuromuscular diseases. While cells in other multicellular organisms have limited functional abilities, the muscle cells and their intracellular components in human subjects are specialized in physiological contraction, relaxation and locomotion. The sarcoplasm contains multiple organelles including mitochondria, sarcoplasmic reticulum, Golgi apparatus, microtubules, glycogens, ribosomes, lipid droplets, and myofibrils. Mitochondria are double-membrane structures located in the sarcoplasm adjacent to the I-band. Axons arise from the cell body at axon hillocks where the thin dendritic process extends. Each axon is surrounded by a plasma membrane called axolemma and contains nuclei and axoplasm; the latter has no ribosomes or rough endoplasmic reticulum. Schwann cells are nucleated spindle cells that envelope axons and serve as electrical conductors. The contain Golgi apparatus, few mitochondria, and scattered inclusions called Reich granules.
The Sodium Action Potential
Anne Feltz in Physiology of Neurons, 2020
The “sodium-only” action potential is found primarily in axons and skeletal muscle fibers; the Ca2+ action potential is found in neuronal cell bodies, smooth muscle, and cardiac muscle. This chapter addresses the Na action potential. In 1938, K. Cole and H. Curtis showed that the membrane conductance of the squid giant axon increased during an action potential. The chapter describes how the presence of voltage-dependent Na and K channels produce the characteristic shape and duration of the sodium action potential. An action potential recorded in the presence of pronase will be longer than an action potential under control conditions. If an action potential is produced at the neuronal cell body, it will propagate the entire length of the axon with the same amplitude and may elicit neurotransmitter release at the axon terminal.
A Role for the Cytoplasmic DEAD Box Helicase Dbp21E2 in Rhodopsin Maturation and Photoreceptor Viability
Published in Journal of Neurogenetics, 2012
Karen L. Hibbard, Joseph E. O'Tousa
Abstract: The Dbp21E2 (DEAD box protein 21E2) is a member of a family of DEAD box helicases active in RNA processing and stability. The authors used genetic mosaics to identify mutants in Dbp21E2 that affect rhodopsin biogenesis and the maintenance of photoreceptor structure. Analysis of a green fluorescent protein (GFP)-tagged Rh1 rhodopsin construct placed under control of a heat shock promoter showed that Dbp21E21 fails to efficiently transport Rh1 from the photoreceptor cell body to the rhabdomere. Retinal degeneration is not dependent on the Rh1 transport defects. The authors also showed that GFP- and red fluorescent protein (RFP)-tagged Dbp21E2 proteins are localized to discrete cytoplasmic structures that are not associated with organelles known to be active in rhodopsin transport. The molecular genetic analysis described here reveals an unexpected role for the Dbp21E2 helicase and provides an experimental system to further characterize its function.
Both early and late apoptotic blebs are taken up by DC and induce IL-6 production
Published in Autoimmunity, 2009
J. H. Fransen, L. B. Hilbrands, C. W. Jacobs, G. J. Adema, J. H. Berden, J. Van Der Vlag
During apo blebs, containing nuclear components, are formed at the cells' surfaces. When these blebs separate from the dying cell an apo cell body remains. The contents of apo blebs are modified and can be released, especially in patients with systemic lupus erythematosus (SLE) since impaired clearance of apo material has been observed in this autoimmune condition. Accordingly, autoantibodies present in subjects with SLE bind to apo blebs. Based on AnxA5 binding, and permeability for PI, we show that apo blebs can be categorized as early (AnxA5+/PI− ) or late (AnxA5+/PI+) apo ones. Both forms of blebs contain apo-induced chromatin modifications and are efficiently phagocytosed by dendritic cell (DC). Uptake by DC of late, but also early apo blebs, stimulate DC to produce IL-6. This bleb-induced effect on DC may be an important step in the initiation of the autoimmune responses in SLE.
Leukocyte transcellular diapedesis: Rap1b is in control
Published in Tissue Barriers, 2015
The neutrophil transmigration across the blood endothelial cell barrier represents the prerequisite step of innate inflammation. It is well known that neutrophils cross the endothelial barrier by transmigrating at the endothelial cell junction (‘paracellular’). However, in vivo and in vitro evidence have clearly demonstrated occurrence of an alternate mode of migration directly through the endothelial cell body (‘transcellular’). Despite our knowledge on mechanisms of transendothelial migration, it remains unclear which factors determine distinct modes of migration. We recently found that the Ras-like Rap1b GTPase limits neutrophil transcellular migration. Rap1b restrains transcellular migration by suppressing Akt-driven invasive protrusions while leaving the paracellular route unaffected. Furthermore, Rap1b limits neutrophil tissue infiltration in mice and prevents hyper susceptibility to endotoxin shock. These findings uncover a novel role for Rap1b in neutrophil migration and inflammation. Importantly, they offer emerging evidences that paracellular and transcellular migration of neutrophils are regulated by separate mechanisms. Here, we discuss the mechanisms of neutrophil transmigration and their clinical importance for vascular integrity and innate inflammation.