Kinetics and voltage dependence of inactivation of a prokaryotic voltage-gated sodium channel (NaChBac) were investigated in an effort to understand its molecular mechanism. NaChBac inactivation kinetics show strong, bell-shaped voltage dependence with characteristic time constants ranging from approximately 50 ms at depolarized voltages to a maximum of approximately 100 s at the inactivation midpoint. Activation and inactivation parameters for four different covalently linked tandem dimer or tandem tetramer constructs were indistinguishable from those of the wild-type channel. Point mutations in the outer part of the pore revealed an important influence of the S195 residue on the process of inactivation. For two mutants (S195D and S195E), the maximal and minimal rates of inactivation observed were increased by approximately 2.5-fold, and the midpoint of the steady-state inactivation curve was shifted approximately 20 mV in the hyperpolarizing direction, compared to the wild-type channel. Our data suggest that pore vestibule structure is an important determinant of NaChBac inactivation, whereas the inactivation mechanism is independent of the number of free cytoplasmic N- and C-termini in the functional channel. In these respects, NaChBac inactivation resembles C-type or slow inactivation modes observed in other voltage-gated K and Na channels.

A single intrathecal injection of 0.2 mg of morphine safely reduces postoperative pain following lumbar fusion.

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Oblique dural puncture was not associated with increased incidence of postoperative CSF leakage. This safe and reliable method of delivery of ITM should therefore be routinely considered in lumbar spine surgery.

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Background Research efforts have been focused on limiting secondary injury after traumatic spinal cord injury by performing spinal decompression and early optimization of spinal cord perfusion. The Winnipeg Intraspinal Pressure Monitoring Study (WISP) was designed to validate the technique of intraspinal pressure monitoring at the site of injury using a fiberoptic pressure monitor placed at the site of injury. Objectives To describe the design of the WISP study. Study design Descriptive. Methods We explain the current limitations in the available scientific literature around the topic of blood pressure management for acute traumatic spinal cord injury and rational for the WISP study. Then, we describe the design of WISP including the patient selection criteria, study interventions, follow up schedules and outcome measurements. A multitude of future research avenues are also discussed. Results The WISP study is a single center pilot study designed to validate the technique of intraspinal pressure monitoring following acute traumatic spinal cord injury. The study involves the measurement of intraspinal pressure from within the subarachnoid space at the site of injury to derive a number of physiological parameters including spinal cord perfusion pressure, spinal cord blood volume, measures of spinal cord compliance and vascular reactivity indices. Twenty eligible patients will be recruited and followed for a period of 12 months with visits scheduled for the first 5 days and 1, 3, 6, and 12 months following surgical intervention. Conclusions The WISP study will provide the first attempt in North America at validation of intraspinal pressure monitoring with a fiberoptic pressure monitor at the site of injury. Successful validation will lead to future studies to define optimal spinal cord perfusion pressure, relationships of neural injury biomarkers and outcomes as well as epigenetic studies. Trial registration This study has been registered at clinicaltrials.gov (registration# NCT04550117).

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