Progress in Neurobiology Vol. 39, pp. 493 to 505, 1992 Printed in Great Britain. All rights reserved
0301-.0082/92/$15.00 ~ 1992PergamonPress Ltd
IONIC C U R R E N T S IN C O C H L E A R HAIR CELLS P. A. FUCHS Department of Physiology, University of Colorado School of Medicine, Denver, CO 80262, U.S.A. (Received I0 January 1992)
CONTENTS I. Introduction 2. The avian cochlea 3. Hair cell excitability 3.1. Electrical tuning at acoustic frequencies 3.2. Low-frequency action potentials 4. Ionic currents 4.1. Voltage-gated calcium current, it, 4.2. Ca-activated K current, l~ca ~ 4.3. Delayed rectifier, I K 4.4. Inward rectifier, /~a 4.5. Inactivating K current, 1^ 4.6. ACh-activated currents, l~^ch~, IKtAch~ 5. Cell-specific distribution of K ~ channels 5.1. Positional variation 5.2. Variation in tall and short cells 6. Conclusions Acknowledgements References
493 494 497 497 497 498 498 498 499 500 501 502 502 502 503 503 504 504
1. I N T R O D U C T I O N Sound waves are converted into bioelectrical signals by the mechanoreceptive ceils (hair ceils) of the cochlea. These contain mechanically-gated ion channels in their apical hair bundle which allow the flux of cations when opened. The mechanism of gating and the character of the transduction channels are areas of recent exciting progress (Hacohen et al., 1989; Crawford et al., 1991). However, this review will focus on ion channels in hair cells that are not transducer channels. Rather, we will consider voltage- and ligand-activated ion channels whose gating is altered subsequent to a change in membrane potential of the hair cell, or upon release of transmitter from efferent neurons that innervate these ceils. These baso-lateral channels serve to shape the receptor potential initiated by the acoustically-gated transducer channels in the apical membrane of the hair cell. Evidence has accumulated that functional distinctions between different hair cells arise at least in part as a consequence of the differential distribution of various of these basolateral ion channels. What types of gated ion channels might one find in hair cells? In addition to providing mechano-transduction, the hair cell also functions as a presynaptic terminal, releasing chemical transmitter onto an associated afferent dendrite. As in nerve terminals, this process requires voltage-gated Ca 2÷ channels and these are found in hair ceils. Inward current also can flow through tetrodotoxin-sensitive, voltage-dependent Na ~ channels that have been reported in a few
hair cells (Evans and Fuchs, 1987; Sugihara and Furukawa, 1989; Sokolowski et al., 1992), but this is by no means common. During acoustic stimulation the presence of voltage-gated Ca 2÷ channels ought to lead to regenerative depolarization. Given this, it seems likely that there might be a mechanism for active repolarization as well, and indeed all hair cells have voltage and ligand-gated K ÷ channels. In fact K ÷ channels provide by far the major conductance, with a striking variety of K ÷ channels presumably serving different functions in different hair cells. Certainly some of these K ÷ channels will counteract sound-evoked depolarization. Perhaps more importantly, open K ÷ channels act to increase the membrane conductance and decrease the membrane time constant, so as to increase the frequency range over which the hair cell's membrane potential can follow a mechanical stimulus. The influence of K ÷ channel activity on hair cell response kinetics has special significance for the phenomenon of electrical tuning found in hair ceils of non-mammalian vertebrates (Crawford and Fettiplace, 1981). Electrical tuning in these cells arises out of the interplay of voltage-gated Ca 2÷ and Ca 2~ -activated K ÷ channels (Lewis and Hudspeth, 1983; Art and Fettiplace, 1987; Fuchs and Evans, 1988; Fuchs et al., 1988; Hudspeth and Lewis, 1988). The kinetics of the Ca2+-activated K channels determines the resonant frequency of each cell (Art and Fettiplace, 1987). In chick cochlear hair ceils electrical tuning as well as other forms of excitability depend on the differential distribution of voltage-dependent, as well
493
494
P.A. t't:fHS
g gKa
~ "~
~ I
g(AChl
gKir gK
gca
FiG. I. Ionic conductances in hair cells. Gr,, carries the voltage-gated, tetrodotoxin-sensitive Na ~ current. GK, is the rapidly inactivating K ÷ conductance that carries "Acurrent". GK(ACh~carries the Ca-activated K + current turned on indirectly by ACh. G(Ac~J carries the cation current
initially activated by ACh. The channels that make up these two ACh-dependent conductances are near one another, and associated with a subsynaptic cistern that is co-extensive with the calyceal efferent synapse. Gc~ carries voltage-gated Ca-~+ c u r r e n t . GKtca t carries "maxi" Ca-activated K* current. Gc, and GKcc-,~are near to one another, and perhaps associated with presynaptic release sites. GKcarries delayed rectifier-type, voltage-gated K + current. GiFtcarries inward (anomalous) rectifier K + current, activated at hyperpolarized membrane potentials. Not all these channel types are found in every hair cell.
cells of turtles, frogs and alligators (Crawford and Fettiplace, 1981; Lewis and Hudspeth, 1983: Ashmore, 1983; Pitchford and Ashmore, 1987; Fuchs and Evans, 1988). In addition, the basilar membrane of birds also demonstrates a mechanically-tuned vibration pattern (von Bekesy, 1960: Gummer et al., 1987) reminiscent of the elaborate and highly specialized mechanical tuning process found in the mammalian cochlea. Thus, the avian cochlea should provide instructive examples of cellular principles of organization also found in other species. Chicken audition ranges from approximately 50 to 5000 Hz, with best sensitivity of 20 dB SPL at 1000 Hz (Gray and Rubel, 1985). The auditory epithelium (basilar papilla) of the chick is contained in an elongated outpocketing of the saccule called the lagena. Although not coiled as in mammals, this 4-5 mm long tube does curve through approximately 120 degrees of arc, and varies in its cellular organization and mechanical characteristics from apex to base, as in mammals. There is a tonotopic pattern of vibration in the chick's cochlea. Low frequency tones vibrate the apex maximally, while progressively higher frequency tones cause maximal vibration nearer to the basal tip (Fig. 2). Ten thousand hair cells (and surrounding supporting cells) cover the basilar membrane (Tilney and Tilney, 1986), and these vary from tall hair cells nearest the neural insertion (Fig. 3), through intermediate forms, to short cells on the free basilar membrane (Fig. 3; see Tanaka and Smith, 1978). Tall and short hair cells correspond in position to inner and outer hair cells of the mammalian cochlea, respectively, and like those,
as Ca2+-activated K* channels (Fuchs et al., 1988; Fuchs and Evans, 1990). Based simply on their prominence and variety, gated K 4 channels appear to be important in the primary function of cochlear hair cells, that is to transduce rapidly varying acoustic sinusoids. Finally, feedback regulation of hair cells by the central nervous system is accomplished through transmitter-gated channels that are also found on the baso-lateral surface. The efferent transmitter substance is thought to be acetylcholine (ACh), but the hair cell cholinergic response is intriguingly different from those known in other cells. Hair cells are hyperpolarized by an ACh-activated K + current, but probably by way of Ca 2+ flux through a nicotinic-like cholinergic receptor (Fuchs and Murrow, 1991, 1992).
'-~.~
BASAL
2. THE AVIAN COCHLEA Ionic currents have been examined in the cochlear hair cells of various mammalian and non-mammalian species, and these will be referred to in context. The principal focus of this review will be recent studies made on hair cells from the chick's basilar papilla ("cochlea"). This will provide continuity in the comparison of specific ion channel types. The chick's basilar papilla appears to be intermediate in form and function between the hearing organs of cold-blooded vertebrates and mammals. Some chick hair cells are electrically tuned (Fuchs et al., 1988) as are the hair
_
o.z
0301-.0082/92/$15.00 ~ 1992PergamonPress Ltd
IONIC C U R R E N T S IN C O C H L E A R HAIR CELLS P. A. FUCHS Department of Physiology, University of Colorado School of Medicine, Denver, CO 80262, U.S.A. (Received I0 January 1992)
CONTENTS I. Introduction 2. The avian cochlea 3. Hair cell excitability 3.1. Electrical tuning at acoustic frequencies 3.2. Low-frequency action potentials 4. Ionic currents 4.1. Voltage-gated calcium current, it, 4.2. Ca-activated K current, l~ca ~ 4.3. Delayed rectifier, I K 4.4. Inward rectifier, /~a 4.5. Inactivating K current, 1^ 4.6. ACh-activated currents, l~^ch~, IKtAch~ 5. Cell-specific distribution of K ~ channels 5.1. Positional variation 5.2. Variation in tall and short cells 6. Conclusions Acknowledgements References
493 494 497 497 497 498 498 498 499 500 501 502 502 502 503 503 504 504
1. I N T R O D U C T I O N Sound waves are converted into bioelectrical signals by the mechanoreceptive ceils (hair ceils) of the cochlea. These contain mechanically-gated ion channels in their apical hair bundle which allow the flux of cations when opened. The mechanism of gating and the character of the transduction channels are areas of recent exciting progress (Hacohen et al., 1989; Crawford et al., 1991). However, this review will focus on ion channels in hair cells that are not transducer channels. Rather, we will consider voltage- and ligand-activated ion channels whose gating is altered subsequent to a change in membrane potential of the hair cell, or upon release of transmitter from efferent neurons that innervate these ceils. These baso-lateral channels serve to shape the receptor potential initiated by the acoustically-gated transducer channels in the apical membrane of the hair cell. Evidence has accumulated that functional distinctions between different hair cells arise at least in part as a consequence of the differential distribution of various of these basolateral ion channels. What types of gated ion channels might one find in hair cells? In addition to providing mechano-transduction, the hair cell also functions as a presynaptic terminal, releasing chemical transmitter onto an associated afferent dendrite. As in nerve terminals, this process requires voltage-gated Ca 2÷ channels and these are found in hair ceils. Inward current also can flow through tetrodotoxin-sensitive, voltage-dependent Na ~ channels that have been reported in a few
hair cells (Evans and Fuchs, 1987; Sugihara and Furukawa, 1989; Sokolowski et al., 1992), but this is by no means common. During acoustic stimulation the presence of voltage-gated Ca 2÷ channels ought to lead to regenerative depolarization. Given this, it seems likely that there might be a mechanism for active repolarization as well, and indeed all hair cells have voltage and ligand-gated K ÷ channels. In fact K ÷ channels provide by far the major conductance, with a striking variety of K ÷ channels presumably serving different functions in different hair cells. Certainly some of these K ÷ channels will counteract sound-evoked depolarization. Perhaps more importantly, open K ÷ channels act to increase the membrane conductance and decrease the membrane time constant, so as to increase the frequency range over which the hair cell's membrane potential can follow a mechanical stimulus. The influence of K ÷ channel activity on hair cell response kinetics has special significance for the phenomenon of electrical tuning found in hair ceils of non-mammalian vertebrates (Crawford and Fettiplace, 1981). Electrical tuning in these cells arises out of the interplay of voltage-gated Ca 2÷ and Ca 2~ -activated K ÷ channels (Lewis and Hudspeth, 1983; Art and Fettiplace, 1987; Fuchs and Evans, 1988; Fuchs et al., 1988; Hudspeth and Lewis, 1988). The kinetics of the Ca2+-activated K channels determines the resonant frequency of each cell (Art and Fettiplace, 1987). In chick cochlear hair ceils electrical tuning as well as other forms of excitability depend on the differential distribution of voltage-dependent, as well
493
494
P.A. t't:fHS
g gKa
~ "~
~ I
g(AChl
gKir gK
gca
FiG. I. Ionic conductances in hair cells. Gr,, carries the voltage-gated, tetrodotoxin-sensitive Na ~ current. GK, is the rapidly inactivating K ÷ conductance that carries "Acurrent". GK(ACh~carries the Ca-activated K + current turned on indirectly by ACh. G(Ac~J carries the cation current
initially activated by ACh. The channels that make up these two ACh-dependent conductances are near one another, and associated with a subsynaptic cistern that is co-extensive with the calyceal efferent synapse. Gc~ carries voltage-gated Ca-~+ c u r r e n t . GKtca t carries "maxi" Ca-activated K* current. Gc, and GKcc-,~are near to one another, and perhaps associated with presynaptic release sites. GKcarries delayed rectifier-type, voltage-gated K + current. GiFtcarries inward (anomalous) rectifier K + current, activated at hyperpolarized membrane potentials. Not all these channel types are found in every hair cell.
cells of turtles, frogs and alligators (Crawford and Fettiplace, 1981; Lewis and Hudspeth, 1983: Ashmore, 1983; Pitchford and Ashmore, 1987; Fuchs and Evans, 1988). In addition, the basilar membrane of birds also demonstrates a mechanically-tuned vibration pattern (von Bekesy, 1960: Gummer et al., 1987) reminiscent of the elaborate and highly specialized mechanical tuning process found in the mammalian cochlea. Thus, the avian cochlea should provide instructive examples of cellular principles of organization also found in other species. Chicken audition ranges from approximately 50 to 5000 Hz, with best sensitivity of 20 dB SPL at 1000 Hz (Gray and Rubel, 1985). The auditory epithelium (basilar papilla) of the chick is contained in an elongated outpocketing of the saccule called the lagena. Although not coiled as in mammals, this 4-5 mm long tube does curve through approximately 120 degrees of arc, and varies in its cellular organization and mechanical characteristics from apex to base, as in mammals. There is a tonotopic pattern of vibration in the chick's cochlea. Low frequency tones vibrate the apex maximally, while progressively higher frequency tones cause maximal vibration nearer to the basal tip (Fig. 2). Ten thousand hair cells (and surrounding supporting cells) cover the basilar membrane (Tilney and Tilney, 1986), and these vary from tall hair cells nearest the neural insertion (Fig. 3), through intermediate forms, to short cells on the free basilar membrane (Fig. 3; see Tanaka and Smith, 1978). Tall and short hair cells correspond in position to inner and outer hair cells of the mammalian cochlea, respectively, and like those,
as Ca2+-activated K* channels (Fuchs et al., 1988; Fuchs and Evans, 1990). Based simply on their prominence and variety, gated K 4 channels appear to be important in the primary function of cochlear hair cells, that is to transduce rapidly varying acoustic sinusoids. Finally, feedback regulation of hair cells by the central nervous system is accomplished through transmitter-gated channels that are also found on the baso-lateral surface. The efferent transmitter substance is thought to be acetylcholine (ACh), but the hair cell cholinergic response is intriguingly different from those known in other cells. Hair cells are hyperpolarized by an ACh-activated K + current, but probably by way of Ca 2+ flux through a nicotinic-like cholinergic receptor (Fuchs and Murrow, 1991, 1992).
'-~.~
BASAL
2. THE AVIAN COCHLEA Ionic currents have been examined in the cochlear hair cells of various mammalian and non-mammalian species, and these will be referred to in context. The principal focus of this review will be recent studies made on hair cells from the chick's basilar papilla ("cochlea"). This will provide continuity in the comparison of specific ion channel types. The chick's basilar papilla appears to be intermediate in form and function between the hearing organs of cold-blooded vertebrates and mammals. Some chick hair cells are electrically tuned (Fuchs et al., 1988) as are the hair
_
o.z
