The ability to detect mechanical energy by activation of specialized ion channels, termed mechano-gated ion channels, is shared by all cellular organisms and underlies the mechanical senses of touch, hearing, and balance. The molecules responsible for these events are not known in any eukaryote. Twelve candidates have been identified by genetic analysis of the response to gentle touch in Caenorhabditis elegans, including three genes (mec-4, mec-6 and mec-10) postulated to encode subunits of the mechano-gated ion channel. Genetic analyses have fostered a detailed model for channel activation which I propose to test using whole-cell electrical recording. Mechano-gated ion currents will be measured in wild-type C. elegans in order to characterize their mechanical sensitivity, ion permeability, and pharmacology. The importance of individual gene products will be studied by measuring mechano-gated ion currents n animals that carry null alleles of the putative ion channel subunits. the effects of defects in genes encoding components of the proposed subcellular scaffold will also be examined. Finally, experiments involving in vitro mutagenesis of putative ion channel subunits and analysis of functional effects by in vivo expression are proposed to identify proteins contributing to the ion pore. The implications of this work lie in the possibility of delineating the molecular components of eukaryotic mechanosensory apparatus and of analyzing their function biophysically in a genetically tractable organism, the nematode C. elegans.
