Signal transduction in hair cells and its regulation by calcium

Ca2+ plays a pivotal role in the regulation of hair cell function. From ,mechanoelectrical transduction at the cell's apex to the release of neurotransmitter at its base, Ca*+ acts continuously to either effect or affect diverse cellular processes. The ability of Ca'+ to perform its various local tasks rests simply on the steep gradients in the activity of Ca*+ that are encountered in the vicinity of open Ca*+ channels (Simon and Llinas, 1985). The sphere of influence of Ca2+ is thus reduced to microdomains, outside of which the ion's activity is probably too low to effect a change in cellular events (Roberts et al., 1990; Llinas et al., 1992; lssa and Hudspeth, 1994). The ion's reach is further restricted by cytoplasmic buffers as well as by ex-trusion mechanisms. Thus, the spatial segregation of the Ca*+ permeation pathways and of the targets of Ca2+ action enables the hair cell to employ the same messenger to convey different messages. Although the involvement of Ca*+ in these processes is unquestioned, our current understanding of the mechanisms by which this influence is exerted remains far from complete. Here, I discuss the role of Ca2+ in several hair cell processes, with particular attention to the light shed on this question by recent work of Denk et al. (1995) and by Tucker and Fettiplace (1995) appearing in this issue (for references and an alternative treatment of these issues , see Lenzi and Roberts, 1994). Mechanoelectrical Transduction The hair bundle, the hair cell's mechanosensitive organ-elle, consists of 30-300 specialized processes named stereocilia, arranged in ranks of increasing height (Figure 1). The rigid stereociliary cytoskeleton is formed by several hu?dred actin filaments, which are cross-linked by fimbrin. Immediately above the stereociliary insertion into the hair cell, this cytoskeleton narrows to just a few dozen filaments. Deflection of the hair bundle in the positive direction (toward its tall end) causes the rigid ster-eocilia to pivot around their slim bases, resulting in shear between their tips. This shear causes the cation-selective transduction channels to open, initiating a chain of events that culminates in the release of transmitter at the base of the cell. The most successful model for mechanoelectrical trans-duction proposes that transduction channels are directly opened by elastic elements, the gating springs, located near the tips of stereocilia. This location has been proposed on the basis of extracellular recordings that place the site of transduction current into the hair …