9514624 Moody Ion channels are proteins that mediate the movement of charged molecules across cell membranes, and thus are responsible for generating the electrical signals used by nerve and muscle cells. The development of excitability in nerve and muscle is governed by complex changes in the populations of ion channels that occur during embryogenesis. It is now clear that in many cells the types and properties of ion channels at early stages of development are very different from those in the mature state. These differences reflect a developmental function for electrical activity, a function that is distinct from the later roles of electrical signaling in the mature cell. By measuring the functional ion channels that are present at different stages of development. we can identify critical periods during which the particular channels present are likely to create spontaneous electrical activity, and then to determine whether that activity is in fact important for later development. Because changes in channel properties during development can be vary rapid, these critical periods can be short, often only a few hours long. In many cells, they can occur before it is possible to identify the cell in the embryo. To understand the biological function of the patterns of ion channel development, therefore, it is necessary to identify cells as early in embryogenesis as possible and to measure the types and properties of ion channels present over a wide range of stages. This project uses electrophysiological recording techniques to measure the properties of ion channels at various stages in the development of a muscle, and molecular techniques to make specific changes in that developmental profile. This will allow determining exactly how electrical activity is influencing development. The results obtained in an accessible experimental system such as frog muscle can then be applied to the development of the mammalian brain, where it is known that electrical activity, often mediated by ear ly sensory experience, plays a role in assuring normal cognitive development.
