Molecular Identity of Nav Channels on Axons

Gene cloning has identified up to 10 different Na channel genes in the mammals, with many expressed in neurons (Goldin, 1999; Goldin et al., 2000). These genes encode sodium channel proteins with similar structural motifs but different kinetic properties due to variation in other regions of their primary amino acid sequence. The location, density, and type of Nav isoforms expressed in myelinated axons greatly affect their physiological responses in health and diseases. The availability of isoform-specific antibodies allows cellular mapping of Nav expression in various normal and pathological axons. Nav1.2 is expressed predominantly in nonmyelinated axons, while Nav 1.6 is expressed predominantly at nodes of Ranvier. Develop-mentally, Nav expression switches from Nav1.2 to Nav1.6 when the axon becomes myelinated (Boiko et al., 2001; Rasband and Trimmer, 2001), a switch that may reflect

Figure 1 Juxtaparanodal clustering of Kv1 channels in mature myelinated axons. (A) Voltage clamp recordings of total ionic currents from a single mammalian node of Ranvier before (left) and after (right) acute paranodal demyelination. Note paranodal demyelination reveals a large outward K current (upward deflections) that is absent in the intact node. Note also that inward Na currents (downward deflections) remain unaffected. (B) Kv1.1 immunofluorescence (green) in a single myelinated fiber, showing juxtaparanodal localization. The fiber is also double-stained with anti-MAG (red). (Reproduced from Chiu, Zhou, Zhang, and Messing, 1999, with permission.)

Figure 1 Juxtaparanodal clustering of Kv1 channels in mature myelinated axons. (A) Voltage clamp recordings of total ionic currents from a single mammalian node of Ranvier before (left) and after (right) acute paranodal demyelination. Note paranodal demyelination reveals a large outward K current (upward deflections) that is absent in the intact node. Note also that inward Na currents (downward deflections) remain unaffected. (B) Kv1.1 immunofluorescence (green) in a single myelinated fiber, showing juxtaparanodal localization. The fiber is also double-stained with anti-MAG (red). (Reproduced from Chiu, Zhou, Zhang, and Messing, 1999, with permission.)

adaptation to a change in firing pattern as axons become myelinated.

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