Santos-Sacchi 1991 — Reversible inhibition of voltage-dependent OHC motility and capacitance

This paper characterized the nonlinear capacitance (NLC) of isolated guinea-pig OHCs — the electrical signature of prestin motor charge movement. Using whole-cell voltage clamp with blocked ionic currents, Santos-Sacchi showed that OHC motility magnitude tracks the NLC-voltage (C-V) curve, that gadolinium reversibly abolishes both, and that NLC is not due to membrane deformation from length change. This paper establishes the biophysical framework for prestin as a voltage-sensitive motor (though prestin was not identified molecularly until 2000).

TL;DR. OHC NLC peaks at −40 mV (AC method, more accurate) or −23 mV step potential from −120 mV holding potential; maximum NLC 16–17 pF; motility and NLC are correlated and both blocked reversibly by 0.5–1 mM gadolinium, dissociating them from pure membrane mechanics.

Key finding. The Boltzmann-shaped C-V function means prestin operates over a wide voltage range (roughly −150 to +50 mV full range); the h02 model simplification of “10 mV threshold” is not in this paper — 10 mV is the signal modulation amplitude assumed sufficient for amplification around the operating point, not a threshold in the Santos-Sacchi framework. V_peak at −40 mV (AC) is the operating point; signals modulate around this.

Numbers that matter

ParameterValueUnitsSource locationConditions
Peak NLC voltage (AC analysis)−40mV (holding potential)AbstractAC method; most physiologically accurate
Peak NLC voltage (step analysis)−23mV (step from −120 mV hold)AbstractStep method; less accurate for V_half
Maximum NLC16–17pFAbstractLow-frequency (apical) OHCs
Maximum charge movementup to 2.5pCAbstractApical OHCs, largest cells
Gadolinium block concentration0.5–1mMAbstractReversible block of both motility and NLC
V_saturationNot reported as single thresholdNLC is Boltzmann; “saturation” is ±2 mV tail of function

Critical note for h02. The script uses “Prestin V_saturation = 70 mV (no citation)” — this is NOT in Santos-Sacchi 1991. The 70 mV value is unsourced. This paper provides V_half ≈ −40 mV and the shape of the Boltzmann, from which a practical saturation range can be calculated, but not a 70 mV discrete threshold.

Limitations

  • Guinea-pig OHCs; mouse prestin (SLC26A5) has similar but not identical kinetics.
  • Holding potential −120 mV is artificial (resting OHC Vm ~−70 mV); step-analysis V_half is shifted from true in-vivo operating point.
  • Gadolinium experiments do not distinguish NLC from prestin-specific effects (Gd³⁺ is a broad-spectrum divalent blocker).

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