A kinetic description of the calcium-activated potassium channel and its application to electrical tuning of hair cells

Wu, Yuh-Cherng; Art, Jonathan; Goodman, Miriam B.; Fettiplace, Robert

doi:10.1016/0079-6107(95)00002-5

Cited by 123 publications

(157 citation statements)

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“…Considerable insight into the mechanism of cooperativity has been obtained by detailed kinetic analysis, which has suggested that the activation of BK channels by Ca 2ϩ and by voltage occurs through separate allosteric mechanisms that modulate the channel opening-closing transitions independently of one another (10,17,18,(20)(21)(22)(23)(24)(25). However, because the gating of BK channels is so complex, it has been necessary in these studies to either make simplifying assumptions about the particular types of the cooperative interactions (10,17,18,(20)(21)(22)25) or to analyze simplified models with fewer assumptions (7,23,24).…”

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confidence: 99%

“…When activated, the efflux of K ϩ out of the cell hyperpolarizes the membrane potential, shutting down voltage-dependent Ca 2ϩ and Na ϩ channels. In this guardian role of controlling Ca 2ϩ influx and excitability, BK channels modulate many processes, such as spike broadening in neurons (3), smooth muscle contraction (4), neurotransmitter release (5), and the electrical tuning of hair cells (6,7). The activation of BK channels by Ca i 2ϩ typically occurs with Hill coefficients of 2-5 (1,(8)(9)(10)(11), indicating that Ca i 2ϩ acts in a highly cooperative manner.…”

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confidence: 99%

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Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Niu

Magleby

2002

Proc. Natl. Acad. Sci. U.S.A.

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BK channels (Slo1) are widely distributed K+ channels that control Ca2+-dependent processes and cellular excitability. Their activation by intracellular Ca2+ (Ca\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}_{i}^{2+}\end{equation*}\end{document}) is highly cooperative, with Hill coefficients of typically 2–5. To investigate the cooperativity contributed by each of the four α subunits that form the BK channel, we studied single channels comprised of mixtures of functional subunits and subunits with a mutation to disrupt a key site (Ca-bowl) required for activation by low concentrations of Ca\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}_{i}^{2+}\end{equation*}\end{document}. As the number of functional subunits increased, we found a stepwise increase in the Hill coefficient of 0.3–0.8 per functional subunit and a stepwise decrease in the Ca\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}_{i}^{2+}\end{equation*}\end{document} required for half activation (Kd). These results show directly that BK channels can open with 0, 1, 2, 3, or 4 functional Ca-bowls, and that each subunit with a functional Ca-bowl contributes a stepwise increase to both the cooperativity of activation and the apparent Ca2+ affinity. A model with 0–4 high-affinity allosteric activators and four low-affinity allosteric activators was examined. In this model, Ca2+ bindings were independent of one another and the cooperativity arose from the joint action of the allosteric activators on the open–closed equilibrium. Although this model described well the major features of the experimental data, some differences between the observed and predicted results indicated that additional factors not included in the model also contribute to the cooperativity

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confidence: 99%

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confidence: 99%

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Niu

Magleby

2002

Proc. Natl. Acad. Sci. U.S.A.

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“…Gradient of membrane excitability along the tonotopic axis is reported in hair cells of several species, including birds (Wu et al, 1995;Ramanathan et al, 1999Ramanathan et al, , 2000Pantelias et al, 2001). In the cochlear nucleus of chicken, Rubel and Parks (1975) demonstrated the tonotopic arrangement in both the NM and NL; NM neurons with lower CF are located in the caudolateral region and those with higher CF in the rostromedial region.…”

Section: Introductionmentioning

confidence: 99%

Tonotopic Gradients of Membrane and Synaptic Properties for Neurons of the Chicken Nucleus Magnocellularis

Fukui¹,

Ohmori²

2004

J. Neurosci.

144

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Nucleus magnocellularis (NM) is a division of the avian cochlear nucleus that extracts the timing of auditory signals. We compared the membrane excitability and synaptic transmission along the tonotopic axis of NM. Neurons expressed a Kv1.1 potassium channel mRNA and protein predominantly in the high characteristic frequency (CF) region of NM. In contrast, the expression of Kv1.2 mRNA did not change tonotopically. Neurons also showed tonotopic gradients in resting potential, spike threshold, amplitude, and membrane rectification. All neurons were sensitive to 100 nM dendrotoxin, but the effects were most significant in the high CF neurons. The EPSC recorded by minimal stimulation of auditory nerve fibers (ANFs) was 13 times larger in high CF neurons than in low CF neurons. Moreover, EPSCs were generated in an all-or-none manner in the high CF neurons when stimulus intensity was increased, whereas EPSCs were graded in the low CF neurons, indicating multiple axonal inputs. ANF synaptic terminals were visualized by DiI. ANF formed enfolding end-bulbs of Held around the cell body in the high and middle CF region but not in the low CF region. These observations indicate coordinated gradients of neuronal properties both presynaptically and postsynaptically along the tonotopic axis. Such specializations may be suitable for extracting and preserving the timing information of auditory signals over a wide range of acoustic frequencies.

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“…Turtle auditory hair cells are an excellent model for identifying factors involved in establishing hair cell resting potential, because their physiological resting potential can be identified by the proper functioning of their major tuning mechanism, electrical resonance (Art et al, 1985;Wu et al, 1995). Electrical resonance is generated by the interaction of BK potassium and L-type calcium channels (Crawford and Fettiplace, 1981;Hudspeth and Lewis, 1988a,b;Wu et al, 1995).…”

Section: Resultsmentioning

confidence: 99%

“…For nonrectified representation of both positive and negative bundle deflections, critical for processing periodic stimuli, the resting open probability of the MET channels must be more than zero. It has been proposed that the inward MET current associated with a nonzero resting open probability should depolarize the hair cell resting potential (Hudspeth and Lewis, 1988b;Wu et al, 1995;Jorgensen and Kroese, 2005). The resting open probability of the channel is established by Ca 2ϩ -dependent adaptation of the MET machinery (Eatock et al, 1987;Crawford et al, 1991;Assad and Corey, 1992;.…”

Section: Introductionmentioning

confidence: 99%

Steady-State Adaptation of Mechanotransduction Modulates the Resting Potential of Auditory Hair Cells, Providing an Assay for Endolymph [Ca²⁺]

Farris¹,

Wells²,

Ricci³

2006

J. Neurosci.

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The auditory hair cell resting potential is critical for proper translation of acoustic signals to the CNS, because it determines their filtering properties, their ability to respond to stimuli of both polarities, and, because the hair cell drives afferent firing rates, the resting potential dictates spontaneous transmitter release. In turtle auditory hair cells, the filtering properties are established by the interactions between BK calcium-activated potassium channels and an L-type calcium channel (electrical resonance). However, both theoretical and in vitro recordings indicate that a third conductance is required to set the resting potential to a point on the I Ca and I BK activation curves in which filtering is optimized like that found in vivo. Present data elucidate a novel mechanism, likely universal among hair cells, in which mechanoelectric transduction (MET) and its calcium-dependent adaptation provide the depolarizing current to establish the hair cell resting potential. First, mechanical block of the MET current hyperpolarized the membrane potential, resulting in broadband asymmetrical resonance. Second, altering steady-state adaptation by altering the [Ca 2ϩ ] bathing the hair bundle changed the MET current at rest, the magnitude of which resulted in membrane potential changes that encompassed the best resonant voltage. The Ca 2ϩ sensitivity of adaptation allowed for the first physiological estimate of endolymphatic Ca 2ϩ near the MET channel (56 Ϯ 11 M), a value similar to bulk endolymph levels. These effects of MET current on resting potential were independently confirmed using a theoretical model of electrical resonance that included the steady-state MET conductance.

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A kinetic description of the calcium-activated potassium channel and its application to electrical tuning of hair cells

Cited by 123 publications

References 58 publications

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Tonotopic Gradients of Membrane and Synaptic Properties for Neurons of the Chicken Nucleus Magnocellularis

Steady-State Adaptation of Mechanotransduction Modulates the Resting Potential of Auditory Hair Cells, Providing an Assay for Endolymph [Ca²⁺]

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A kinetic description of the calcium-activated potassium channel and its application to electrical tuning of hair cells

Cited by 123 publications

References 58 publications

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca 2+

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca 2+

Tonotopic Gradients of Membrane and Synaptic Properties for Neurons of the Chicken Nucleus Magnocellularis

Steady-State Adaptation of Mechanotransduction Modulates the Resting Potential of Auditory Hair Cells, Providing an Assay for Endolymph [Ca2+]

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Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca ²⁺

Steady-State Adaptation of Mechanotransduction Modulates the Resting Potential of Auditory Hair Cells, Providing an Assay for Endolymph [Ca²⁺]