Biomedical subjects

I Vabnick

Publications and source records attributed to I Vabnick.

4 recordsLinked to original sources

PubMed1999

Dynamic potassium channel distributions during axonal development prevent aberrant firing patterns.

The distribution and function of Shaker-related K+ channels were studied with immunofluorescence and electrophysiology in sciatic nerves of developing rats. At nodes of Ranvier, Na+ channel clustering occurred very early (postnatal days 1-3). Although K+ channels were not yet segregated at most of these sites, they were directly involved in action potential generation, reducing duration, and the refractory period. At approximately 1 week, K+ channel clusters were first seen but were within the nodal gap and in paranodes, and only later (weeks 2-4) were they shifted to juxtaparanodal regions. K+ channel function was most dramatic during this transition period, with block producing repetitive firing in response to single stimuli. As K+ channels were increasingly sequestered in juxtaparanodes, conduction became progressively insensitive to K+ channel block. Over the first 3 weeks, K+ channel clustering was often asymmetric, with channels exclusively in the distal paranode in approximately 40% of cases. A computational model suggested a mechanism for the firing patterns observed, and the results provide a role for K+ channels in the prevention of aberrant excitation as myelination proceeds during development.

Action Potentials↗

PubMed1998

Ion channel redistribution and function during development of the myelinated axon.

The development of myelinated axons represents one of the most complex interactions among different cell types in the nervous system. Striking changes occur in both morphology and function in the early postnatal period. Myelination effectively isolates electrically most of the axolemma and dramatically alters the pathways for current flow that are required for rapid, reliable, and efficient conduction. Correspondingly, ion channels must be directed to and stabilized at their required sites. In the case of Na+ channels, this requires a 25-fold increase in density within nodes of Ranvier, and, in mammalian fibers, a virtually complete spatial separation from voltage-dependent K+ channels. Nodes must also be properly spaced to ensure a high conduction velocity and energy efficiency without compromising the safety factor for reliable propagation. In this review, we consider the events responsible for axon development, emphasizing the involvement of ion channels. We discuss the current state of research in this area, including some controversies regarding mechanisms of neuron-glial communication.

Animals↗

PubMed1997

Sodium channel distribution in axons of hypomyelinated and MAG null mutant mice.

Na+ channel organization was studied with immunofluorescence in the peripheral nervous system of mice genetically altered to produce abnormal myelin. In two of these strains, transcription of inserted transgenes was targeted to myelinating Schwann cells through linkage to a promoter for the myelin protein P0. Adults of both of these strains had hindlimb paralysis and a tremor on lifting by the tail. In one case, Schwann cells were eliminated via expression of the diphtheria toxin A chain (DT-A). During postnatal days 3-7, Na+ channel clustering at forming nodes was dramatically reduced compared with that of normal animals. At 1-3 months of age, Na+ channel immunofluorescence was often found spread over long stretches of the axolemma, instead of being confined to nodal gaps. In the second P0-linked transgenic model, Schwann cell expression of the large T antigen tsA-1609 resulted in cell cycle dysfunction. Adult axons had regions of diffuse Na+ channel labeling. Focal clusters were rare within these zones, which were characterized by a series of cells of myelinating phenotype tightly apposed to the axon. Previous studies suggested that Schwann cells had to reach the stage of ensheathment characterized by periaxonal myelin associated glycoprotein (MAG) expression in order to induce Na+ channel clustering. However, in MAG-deficient mice, Na+ channel labeling patterns within sciatic nerves were normal.

Aging↗

PubMed1996

The clustering of axonal sodium channels during development of the peripheral nervous system.

The distribution of Na+ channels in rat peripheral nerve was measured during development by using immunofluorescence. Small segments of sciatic nerve from postnatal day 0-13 (P0-P13) pups were labeled with an antibody raised against a well conserved region of the vertebrate Na+ channel. At day P0 axons contained almost no Na+ channel aggregates. The number of clusters increased dramatically throughout the first week. In almost all cases Na+ channels clustered in the vicinity of Schwann cell processes. At least four classes of aggregates were noted. Clusters formed singly at Schwann cell edges, in pairs or in broad regions between neighboring Schwann cells, and in more focal zones at presumptive nodes. Almost all Na+ channel aggregates had reached the latter stage by the end of the first week. Histograms plotting the frequency of occurrence of each cluster type suggested a sequence of events in node formation involving the initiation of channel aggregation by Schwann cell processes. The requirement for Schwann cells during sodium channel clustering was tested by blocking proliferation of these cells with the antimitotic agent mitomycin C. Na+ channel clustering was sharply reduced, whereas node formation was normal at a distal site along the same nerve. Immunocytochemical detection of myelin-associated glycoprotein (MAG) indicated that Schwann cells must begin to ensheathe axons before inducing Na+ channel clustering.

Aging↗