Calcium Currents in Hair Cells Isolated from Semicircular Canals of the Frog

Abstract

L-type and R-type Ca(2+) currents were detected in frog semicircular canal hair cells. The former was noninactivating and nifedipine-sensitive (5 microM); the latter, partially inactivated, was resistant to omega-conotoxin GVIA (5 microM), omega-conotoxin MVIIC (5 microM), and omega-agatoxin IVA (0.4 microM), but was sensitive to mibefradil (10 microM). Both currents were sensitive to Ni(2+) and Cd(2+) (>10 microM). In some cells the L-type current amplitude increased almost twofold upon repetitive stimulation, whereas the R-type current remained unaffected. Eventually, run-down occurred for both currents, but was prevented by the protease inhibitor calpastatin. The R-type current peak component ran down first, without changing its plateau, suggesting that two channel types generate the R-type current. This peak component appeared at -40 mV, reached a maximal value at -30 mV, and became undetectable for voltages > or =0 mV, suggestive of a novel transient current: its inactivation was indeed reversibly removed when Ba(2+) was the charge carrier. The L-type current and the R-type current plateau were appreciable at -60 mV and peaked at -20 mV: the former current did not reverse for voltages up to +60 mV, the latter reversed between +30 and +60 mV due to an outward Cs(+) current flowing through the same Ca(2+) channel. The physiological role of these currents on hair cell function is discussed.

Functional Interaction of Auxiliary Subunits and Synaptic Proteins With CaV1.3 May Impart Hair Cell Ca2+Current Properties

“…Figure 1 shows examples of Ca 2ϩ current traces generated from hair cells. In agreement with earlier studies (Hudspeth and Lewis 1988;Martini et al 2000;Smotherman and Narins 1999;Zidanic and Fuchs 1995), the DHP-sensitive Ca 2ϩ current in hair cells has a rapid onset and inactivates slowly. Despite the fact that the channel has been identified as Ca V 1.3␣ 1 channel (Kollmar et al 1997a), the current profile of the expressed-channel in HEK 293 cells is in sharp contrast to that in hair cells.…”

Null Mutation of ?1D Ca2+ Channel Gene Results in Deafness but No Vestibular Defect in Mice

“…Finally, neurotransmitter release by hair cells onto afferent nerve terminals of the vestibular nerve is mediated by Ca 2+ entry via presynaptic VGCCs. Although the nimodipine-sensitive Ca 2+ current contributes substantially to the VGCC in vestibular hair cells (Hudspeth and Lewis 1988;Prigioni et al 1992;Martini et al 2000;Rispoli et al 2001), our behavioral and electrophysiological analyses of the vestibular system of the a 1D )/) mice show that in addition, there is a non-nimodipine-sensitive current. In contrast to the auditory system, the vestibular hair cells employ multiple VGCCs that mediate neurotransmitter release to ensure proper balance.…”

“…ever, recent reports have demonstrated that hair cells in lower vertebrates and mammals do express nimodipine-insensitive Ca 2+ currents (Su et al 1995;Martini et al 2000;Platzer et al 2000;RodriguezContreras and Yamoah 2001). Although the functions of the non-L-type current remain unclear, their voltage-dependent properties suggest a possible function in tonic release of neurotransmitters (Martini et al 2000;Rodriguez-Contreras and Yamoah 2001).…”

“…Although the functions of the non-L-type current remain unclear, their voltage-dependent properties suggest a possible function in tonic release of neurotransmitters (Martini et al 2000;Rodriguez-Contreras and Yamoah 2001). Measurements of hair cell capacitance as an index for exocytotic release of neurotransmitters from hair cells have shown that the nimodipine-sensitive component of the whole-cell Ca 2+ (L-type) current plays a marked role in phasic neurotransmitter release.…”

“…The fast neurotransmitter release in hair cells relies on the voltage-and time-dependent properties of clusters of a 1D Ca 2+ channels at the release sites (RodriguezContreras and Yamoah 2001;Rispoli et al 2001). Moreover, the whole-cell current activates at low membrane voltages ()50 mV), has a fast activation time constant (0.5 ms), and has half-activation voltages ranging from )40 to +20 mV (Hudspeth and Lewis 1988;Zidanic and Fuchs 1995;Martini et al 2000;Platzer et al 2000;Rodriguez-Contreras and Yamoah 2001). Furthermore, hair cells may express not only a 1D Ca 2+ channels alone, but several other distinct Ca 2+ channels as well, ensuring multiple Ca 2+ -dependent processes.…”