Fig. 5. Schematic representation of an inner ear sensory cell and proposed molecular model of the slow adaptation process. (A) The hair bundle is composed of 20-300 actin-filled stiff microvilli, called the stereocilia, arranged in three to four rows of increasing height. Stereocilia are held together by different types of lateral links. In addition, a single tip link joins the tip of each stereocilium to the lateral side of its taller neighbour in the adjacent row. (B) According to the gating spring hypothesis (Howard and Hudspeth, 1987), deflection of the hair bundle in the excitatory direction exerts a tension force on the tip links. The force is transmitted to the mechanoelectrical transduction (MET) channels (believed to be located close to the tip link insertion in the membrane), increasing their probability of being open. An influx of cations (mainly K⁺ ions, but also Ca²⁺ ions) through the open MET channels depolarises the hair cell leading to neurotransmitter release and signalling to the central nervous system via afferent nerve fibres. (C) A model of the slow adaptation process evoked by sustained deflection of the hair bundle. The Ca²⁺ influx through the open MET channels triggers the adaptation process (see Fettiplace and Ricci, 2003; Gillespie and Cyr, 2004). The increase of the stereociliar Ca²⁺ concentration weakens calmodulin (CaM) binding to the myosin 1c IQ motifs, which in turn interact with anionic phospholipids [such as PtdIns(4,5)P₂ (PIP₂)] in the membrane. This also leads to the dissociation of myosin molecules from actin filaments. The resulting reduction in the tension exerted on the stereocilia membrane is thought to underlie the slow adaptation process, i.e. a decrease of the MET channel open probability while the mechanical stimulus is persisting. The PHR1-myosin complexes are expected to function as elastic molecular crosslinkers that contribute to and modulate the membrane tension. Unlike myosin 1c-phospholipids interactions, they may not be dependent on the local Ca²⁺ concentration.