Molecular and Functional Characterization of Neuronal FMRFamide-Activated Channels

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IBN 98-10804 PRICE Many of the cells that compose an animal communicate with each other by means of chemical signals. One cell releases a chemical which is detected by another cell through the interaction of the chemical with a "receptor" protein on the cell's surface. The receptor must pass the external signal into the interior of the cell and often does so by opening a selective pore in the cell's surface which lets particular charged ions into and out of the cell. The selective pore is called an "ion channel" and the receptor is said to "gate" the channel. Such signaling is especially elaborate in the nervous system, but ion channels are also involved in salt and water balance and are particularly abundant in the kidney. One of the kidney channels is called the epithelial sodium channel because it allows the sodium ion to pass. It was thought that the epithelial sodium channels were completely distinct from sodium channels mediating chemical signal transmission in the nervous system, but it has recently been shown that one type of channel in the nervous system is related to the epithelial sodium channels. In the snail Helix, one such epithelial sodium-channel relative from the nervous system is gated by a particular chemical named FMRFamide. FMRFamide is a peptide released by certain nerve cells and is thus one example of a group of signaling molecules known as neuropeptides. FMRFamide is the only neuropeptide known to directly gate an ion channel and the channel it gates is the only epithelial sodium channel relative known to be gated by a substance released by nerve cells (i.e. by a "neurotransmitter"). Dr. Price has cloned portions of two epithelial sodium channels from the sea slug Aplysia (an animal related to the land-snail, Helix, but with a much more extensively studied nervous system than Helix). He will now try to isolate full length clones (cultured cells containing the gene from Aplysia) containing these two channels so that their physica l properties can be determined and also so that their localization in the nervous system can be compared to the known localization of FMRFamide. The end result of these studies will be a better understanding of how neuropeptides are involved in the communication of individual nerve cells of an animal and how such communication mediates the complex behaviors that even the most simple animals exhibit.