Developmental expression and functions of voltage-gated potassium channels in normal and mutant mice
Hallows, Janice Lynn, 1956-
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Kv1.1, a Shaker-like voltage-gated potassium channel, is strongly expressed in a variety of neurons in adult rodents, where it appears to be involved in regulating neuronal excitability. Here we show that Kv1.1 is also expressed during development in the mouse, and undergoes very complex changes in expression and localization during both embryonic and postnatal development.In the embryo, there are two transient peaks of Kv1.1 expression, occurring around embryonic day (E) 9.5 and E14.5. At E9.5, Kv1.1 RNA and protein are detected transiently in non-neuronal cells in tightly restricted segments or regions of the early central nervous system, including rhombomeres 3 and 5, the mesencephalon and the diencephalon. At E14.5, several cell types in both the central and peripheral nervous systems express Kv1.1, including neuronal cells (sensory ganglia and outer aspect of cerebral hemispheres) and glial cells (radial glia, satellite cells, Schwann cell precursors). These data show that Kv1.1 is expressed transiently in a variety of neuronal and non-neuronal cells during restricted periods of embryonic development, and the expression pattern suggests several potential developmental roles for Kv1.1. Using mice lacking both copies of Kv1.1, we have found that this channel appears to be involved in the regulation of Schwann cell proliferation.During postnatal development, Kv1.1 and Kv1.2 undergo a dramatic redistribution in peripheral nerves. We show here that this redistribution is a very dynamic process that involves the formation of characteristic intermediate clusters and occurs over several days time. The cues or signals responsible for the redistribution of Kv channels remain unknown. To begin to understand these signals, we have examined the distribution of both Kv1.1 and voltage-gated sodium (Na) channels in the neurological mouse mutant quivering. We report here that both types of ion channels are mislocalized in the sciatic nerves of mice with three different alleles of quivering. Second, peripheral myelin is disrupted in at least one of the quivering alleles. Finally, the degree of anatomical disruption in these mice correlates with the severity of the hindlimb phenotype in quivering mice.
- Pharmacology