The long-term goal of this research is to understand the molecular basis of ion conduction and selectivity in K+ channels and cyclic nucleotide-gated channels. K+ channel studies focus on the voltage-gated Shaker K+ channel derived from Drosophila melanogaster and the inward rectifier K+ channel ROMK1 derived from mammalian kidney. The cyclic nucleotide gated channel is from fish olfactory neurons. These channels will be expressed in Xenopus oocytes and studied using two-electrode voltage clamp and patch-recording techniques. Mutations of the pore-forming amino acids will be produced using molecular biological methods and the functional consequences studied. The experiments aim to understand the physical-chemical mechanisms by which selective ion channels recognize and bind the appropriate ions in their pores. The K+ channels and cyclic nucleotide-gated cation channels provide a valuable contrast because although they are members of a common gene superfamily, they have distinct ion selectivity properties. The channels under study are homologs of channels present in humans. The K+ channels underlie a variety of cellular processes including electrical impulse propagation and control of the cell membrane resting potential - both are important to the physiology of cardiovascular and neurological systems. The cyclic nucleotide-gated channels mediate visual and olfactory sensory transduction. This research may open the way, in the future, to the development of pharmacological agents directed against these important proteins.
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