The long-term objective of our research is to understand the developmental regulation of ion channels during early embryogenesis. The ontogeny of electrical excitability involves more than the synthesis and insertion of ion channels during terminal differentiation, since in most animals the unfertilized oocyte has voltage-gated ion channels similar to those found in mature excitable cells. Only recently has the completely with which these channels are regulated during early embryogenesis been recognized. and the mechanisms responsible have received much less attention than their counterparts in mature cells. The biological significance of channel modulation in embryos is not well understood, but the complex patterns of modulation that occur over long periods of development suggest that the proper integration of changes in ton channel properties with developmental events is an essential part of embryogenesis. We study this problem in ascidian embryos. Ascidians are advanced marine invertebrates, classified in the same phylum (Chordata) as mammals. The small cell number, identifiability of cells, early commitment of cell fates, and well-described fate maps make them very useful for electrophysiological studies. The particular species we use has an endogenous orange pigment that marks muscle-lineage cells and allows them to be identified visually at very early stages. This has allowed us to describe differentiation of ion channel populations in muscle that occurs long before overt morphological differentiation. To map changes in ton channel properties during embryogenesis, we isolate identified cells from various stages and use the whole-cell patch clamp technique. Our results show numerous examples of specific modulation of ion channels at defined developmental stages. Our proposed experiments have two goals: (1) to investigate the mechanisms by which changes in ion channel properties occur and are coordinated with other events of development, and (2)to test the hypothesis that this tight coordination reflects a developmental function for the channels involved. These experiments are directly relevant to diseases in which abnormalities occur in the development of cell electrical properties.
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