Gerbils can tune in
2008-02-15

Mammals have developed a unique sense of hearing with astonishing sensitivity and the largest frequency range among vertebrates. Frequency representation in mammals is achieved by mechanical tuning of the cochlea, caused mainly by geometrical and stiffness gradients of the basilar membrane changing from the cochlear base (where high frequencies are represented) towards the apex (low frequencies). Incoming sound causes motion of the cochlear partition at a place dependent on the frequency of the signal, which is enhanced and sharpened by the unique electromotility of outer hair cells (OHC; Davis, 1983). By this mechanical filtering the sound is band-pass filtered with a band width that is proportional to the centre frequency of the filter. In turn, the inner hair cells (IHCs) in that region are excited and relay the band-pass filtered acoustic information to the brain. In contrast to mammals, frequency encoding in the auditory organ of lower vertebrates (the basilar papilla) is accomplished by intrinsic tuning of hair cells. These cells exhibit gradients in their electrical properties, such as number and kinetics of Ca2+ and Ca2+-activated K+ channels. Therefore, a particular hair cell with a given channel composition will respond best to sound of a specific frequency with oscillations of its receptor potential that match the stimulus frequency (for review, see Fettiplace & Fuchs, 1999). Since the oscillatory response of the receptor potential is limited by low-pass filter characteristics of the hair cells, the frequency range over which amphibia, reptiles and birds hear is much smaller than that of most mammals. As mammals have developed mechanical cochlear tuning that analyses the sound spectrum before it is transduced by the opening of mechano-sensitive channels at the hair cell's stereocilia they do not show electrical tuning. Interestingly enough, mammalian hair cells – especially OHCs– show graded geometric/structural properties along the tonotopic axis of the cochlea, such as cell length or stereocilia bundle height. Only recently have functional gradients as well as properties restricted to either the lower or the higher frequency range been established for OHCs (He et al. 2004; Engel et al. 2006). In the present issue of The Journal of Physiology, Johnson & Marcotti (2008) for the first time provide evidence that IHCs also show functional gradients along the cochlear length. The authors used the gerbil cochlea, which spans a frequency range of ∼200–50 000 Hz, and analysed biophysical properties of IHC Cav1.3 Ca2+ currents at either end of the organ of Corti. Cav1.3 channels form the predominant voltage-activated Ca2+ channels in mammalian IHCs and are indispensable for exocytosis (Platzer et al. 2000; Brandt et al. 2003). Using conditions mimicking the physiological situation as closely as possible – body temperature and 1.3 mm extracellular Ca2+, Johnson & Marcotti demonstrated that apical (low frequency) IHCs display Ca2+ currents with relatively slower activation kinetics compared with basal (high frequency) cells. Activation time constants differed by a factor of almost two at potentials of –57 mV, close to the resting potential of the IHCs at the hearing threshold. The authors also showed a tonotopic difference in the degree of Ca2+ current inactivation in adult gerbils, which was more pronounced in basal IHCs. In mature IHCs, sound elicits a depolarizing transducer current that activates Ca2+ and K+ channels. Though the contribution of the small Cav1.3 current to the receptor potential can be neglected it provides the Ca2+ signal for exocytosis. Any gradient of Cav1.3 activation time constants in the physiologically relevant voltage range, e.g. negative to –20 mV, will affect the speed at which transmitter is released at different cochlear locations. Both receptor potential and transmitter release from the IHC are phase-locked to the sound stimulus at frequencies below 2.5–5 kHz (Palmer & Russell, 1986), a mechanism that is essential for pitch perception and sound source localization. Above that frequency, IHCs relay mainly envelope information of the sound signal, which nevertheless can be temporally modulated with frequencies up to approximately half the bandwidth of the cochlear filter, leading to modulation frequencies in the kilohertz range. The gradient in time constants of Ca2+ current activation may therefore help to ensure phase locking to the stimulus at lower frequencies and to the temporal modulation of the envelope at higher frequencies. A tonotopic difference in Ca2+ current activation time constants was also found by Johnson & Marcotti in immature IHCs, even though current activation speeded up in adult cells of either location. In prehearing IHCs, which do not yet receive sound stimuli, Cav1.3 currents are essential for generating Ca2+ action potentials that are assumed to control IHC maturation and proper connectivity of higher auditory nuclei. Tonotopic differences in Ca2+ channel properties in prehearing IHCs may specifically serve the requirements of high- and low-frequency developmental paradigms. The developmental and locational differences in Ca2+ channel properties moreover imply that the molecular composition of Cav1.3 channels must change during development according to cochlear location, for example by using alternative Cav1.3 splice variants, auxiliary subunits or modulatory proteins. While in most rodents, including rats and mice, hearing starts above 1 kHz, gerbils have an unusually low-frequency hearing range (down to ∼200 Hz). The tonotopic gradients in IHC physiology shown by Johnson & Marcotti are of great interest for understanding sound coding in mammals with a lower frequency hearing range, especially in humans. We must wait to see if IHC tuning, so elegantly shown here for the gerbil, is also present in other mammals.