Abstract
Professional deep-water divers, exposed to hyperbaric pressure (HP) above 1.1 MPa, develop High Pressure Neurological Syndrome (HPNS), which is associated with central nervous system (CNS) hyperexcitability. It was previously reported that HP augments N-methyl-D-aspartate receptor (NMDAR) synaptic response, increases neuronal excitability and potentially causes irreversible neuronal damage. Our laboratory has reported differential current responses under HP conditions in NMDAR subtypes that contain either GluN1-1a or GluN1-1b splice variants co-expressed in Xenopus laevis oocytes with all four GluN2 subunits. Recently, we reported that the increase in ionic currents measured under HP conditions is also dependent on which of the eight splice variants of GluN1 is co-expressed with the GluN2 subunit. We now report that the NMDAR subtype that contains GluN1-4a/b splice variants exhibited “dichotomic” (either increased or decreased) responses at HP. The distribution of the results is not normal thus analysis of variance (ANOVA) test and clustering analysis were employed for statistical verification of the grouping. Furthermore, the calculated constants of alpha function distribution analysis for the two groups were similar, suggesting that the mechanism underlying the switch between an increase or a decrease of the current at HP is a single process, the nature of which is still unknown. This dichotomic response of the GluN1-4a/b splice variant may be used as a model for studying reduced response in NMDAR at HP. Successful reversal of other NMDAR subtypes response (i.e., current reduction) may allow the elimination of the reversible malfunctioning short term effects (HPNS), or even deleterious long term effects induced by increased NMDAR function during HP exposure.
Highlights
Diving to depths of more than 50 m of seawater, (0.1 MPa = 1 ATA ∼= 10 msw) is considered as deep diving and is mainly used for occupational and military purposes
Hydrostatic hyperbaric pressure (HP) above 1.1 MPa causes High Pressure Neurological Syndrome (HPNS; Bennett and Rostain, 2003), which is characterized by reversible central nervous system (CNS) hyperexcitability and cognitive and motor deficits
Each N-methyl-D-aspartate receptor (NMDAR) subtype was tested with at least two separate batches of oocytes obtained from different frogs, while each batch showed the two types of responses
Summary
Professional divers in the oil industry perform dives to depth of 200 msw (2.1 MPa) or even deeper in order to maintain and recover oil platform equipment. The deepest test dive was made in a dry pressure chamber to a depth of 701 msw (7.05 MPa) by the company Comex in 1992 (Lafay et al, 1995). Under such condition professional divers may suffer from direct hyperbaric pressure (HP) effects that present many physiological challenges, affecting the lungs, viscera, and nervous system. In addition to HPNS, prolonged repetitive deep sea operations of professional divers at HP may result in permanent memory and motor impairment (Gronning and Aarli, 2011)
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