CaltechTHESIS
  A Caltech Library Service

The Ionic Basis of Frequency Selectivity in Hair Cells of the Bullfrog's Sacculus

Citation

Lewis, Richard Sheridan (1985) The Ionic Basis of Frequency Selectivity in Hair Cells of the Bullfrog's Sacculus. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/MZGR-KW63. https://resolver.caltech.edu/CaltechTHESIS:04262016-091328237

Abstract

Hair cells from the bull frog's sacculus, a vestibular organ responding to substrate-borne vibration, possess electrically resonant membrane properties which maximize the sensitivity of each cell to a particular frequency of mechanical input. The electrical resonance of these cells and its underlying ionic basis were studied by applying gigohm-seal recording techniques to solitary hair cells enzymatically dissociated from the sacculus. The contribution of electrical resonance to frequency selectivity was assessed from microelectrode recordings from hair cells in an excised preparation of the sacculus.

Electrical resonance in the hair cell is demonstrated by damped membrane-potential oscillations in response to extrinsic current pulses applied through the recording pipette. This response is analyzed as that of a damped harmonic oscillator. Oscillation frequency rises with membrane depolarization, from 80-160 Hz at resting potential to asymptotic values of 200-250 Hz. The sharpness of electrical tuning, denoted by the electrical quality factor, Qe, is a bell-shaped function of membrane voltage, reaching a maximum value around eight at a membrane potential slightly positive to the resting potential.

In whole cells, three time-variant ionic currents are activated at voltages more positive than -60 to -50 mV; these are identified as a voltage-dependent, non-inactivating Ca current (Ica), a voltage-dependent, transient K current (IA), and a Ca-dependent K current (Ic). The C channel is identified in excised, inside-out membrane patches on the basis of its large conductance (130-200 pS), its selective permeability to Kover Na or Cl, and its activation by internal Ca ions and membrane depolarization. Analysis of open- and closed-lifetime distributions suggests that the C channel can assume at least two open and three closed kinetic states.

Exposing hair cells to external solutions that inhibit the Ca or C conductances degrades the electrical resonance properties measured under current-clamp conditions, while blocking the A conductance has no significant effect, providing evidence that only the Ca and C conductances participate in the resonance mechanism. To test the sufficiency of these two conductances to account for electrical resonance, a mathematical model is developed that describes Ica, Ic, and intracellular Ca concentration during voltage-clamp steps. Ica activation is approximated by a third-order Hodgkin-Huxley kinetic scheme. Ca entering the cell is assumed to be confined to a small submembrane compartment which contains an excess of Ca buffer; Ca leaves this space with first-order kinetics. The Ca- and voltage-dependent activation of C channels is described by a five-state kinetic scheme suggested by the results of single-channel observations. Parameter values in the model are adjusted to fit the waveforms of Ica and Ic evoked by a series of voltage-clamp steps in a single cell. Having been thus constrained, the model correctly predicts the character of voltage oscillations produced by current-clamp steps, including the dependencies of oscillation frequency and Qe on membrane voltage. The model shows quantitatively how the Ca and C conductances interact, via changes in intracellular Ca concentration, to produce electrical resonance in a vertebrate hair cell.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Hair cell, frequency tuning, ion channels, modeling
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Neurobiology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Hudspeth, A. James (advisor)
  • Horn, Richard J. (co-advisor)
Thesis Committee:
  • Berg, Howard C. (chair)
  • Kennedy, Mary B.
  • Lester, Henry A.
  • Hudspeth, A. James
  • Horn, Richard J.
Defense Date:2 July 1984
Non-Caltech Author Email:rslewis (AT) stanford.edu
Funders:
Funding AgencyGrant Number
NIHNS13154
NIHGM07737
System Development FoundationUNSPECIFIED
CaltechUNSPECIFIED
Jean Weigle Memorial FundUNSPECIFIED
Record Number:CaltechTHESIS:04262016-091328237
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:04262016-091328237
DOI:10.7907/MZGR-KW63
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/304538a0DOIArticle adapted for Chapter One.
https://doi.org/10.1007/978-3-642-69257-4_3DOIConference paper adapted for Appendix.
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9686
Collection:CaltechTHESIS
Deposited By: Benjamin Perez
Deposited On:26 Apr 2016 17:06
Last Modified:20 Dec 2019 19:43

Thesis Files

[img]
Preview
PDF - Final Version
See Usage Policy.

56MB

Repository Staff Only: item control page