Boltzmann analysis of CM waveforms using virtual instrument software

Ion flow in cochlear hair cells and the regulation of hearing sensitivity

“…For IHCs, the MET operating point is far to one side of the Boltzmann curve (with a small percentage of MET channels open in silence), producing high-efficiency rectification and a net depolarization during sound. In OHCs, however, the MET operating point is much closer to the center of the OHC Boltzmann function (due to autoregulation), with just over 50% of the MET channels open in silence (Patuzzi and O'Beirne, 1999), and the rectification efficiency is very low, with OHCs producing only a small negative DC receptor potential for high-frequency stimulation (Cody and Russell, 1987).…”

“…This is particularly true in the cochlea, where important components are highly nonlinear, and large but slow fluctuations in variables like cochlear fluid pressure or the endocochlear potential (EP) can bias the operating points on key nonlinearities, modulating small-signal gain and hearing threshold (see Patuzzi et al, 1989). Because the overall positive feedback of OHCs depends on forward transduction (mechano-electrical transduction or MET; see Holton and Hudspeth, 1986) that produces an oscillatory (AC) membrane potential to drive the prestin electromotility, the OHCs require complex molecular machinery to stabilize (at least) two crucial variables: their resting membrane potential at about À60 mV (near the optimum voltage for the nonlinear electromotility of prestin, and sufficiently negative to assist K þ entry for efficient MET), and their hair bundle angle and MET opening probability at about 50% for optimal MET sensitivity (Patuzzi and O'Beirne, 1999). To allow both forms of regulation, the OHCs require interconnected feedback loops (see Fig.…”

“…Note also the two types of Ca 2þ sacs within the OHCs, and the Ca 2þ microdomains between the sacs and the basolateral walls of the OHCs. and 4) and (b) by pre-biasing their apical MET to nearly its midpoint (Patuzzi and O'Beirne, 1999), producing maximum AC efficiency but only small DC receptor potentials, little net change in K þ flux with sound (in the cochlear base at least), little sound-evoked Cl À entry and minimal cell swelling.…”

Non-Linear Aspects of Outer Hair Cell Transduction and the Temporary Threshold Shifts after Acoustic Trauma

“…As a result, the transfer curve relating the apical conductance of outer hair cells (OHCs) to hair bundle angle follows a sigmoidal Boltzmann activation curve. The non-linear Boltzmann curve describing the opening and closing of the MET channels of the OHCs of the guinea pig cochlea can be estimated from the low-frequency microphonic potential, V cm , recorded in the fluid surrounding these cells, with the cochlear microphonic (CM) given by V cm = V sat /[1 + exp(Z(P -P o )/kT)], with V sat representing the saturated amplitude of the CM at high sound levels, Z representing the sensitivity of the channels to pressure fluctuations, and P o representing the operating point on the Boltzmann curve at zero crossings of the sinusoidal pressure stimulus [Patuzzi and Moleirinho, 1998;Patuzzi and O'Beirne, 1999]. A drop in the saturation parameter V sat can be produced by a drop in the driving potential for the OHC receptor current (a drop in endocochlear potential, for example), a drop in the number of functional MET channels or OHCs, or a drop in the conductance of the basolateral wall of the OHCs.…”

“…Changes in the operating parameter P o can be due to slow changes in the angle of the OHC hair bundle, produced by hydrostatic and osmotic changes within the organ of Corti, active changes in OHC length due to changes in OHC membrane potential or intracellular calcium, and probably other molecular changes associated with the MET channels and their environment. We briefly describe the use of software to analyse the low-frequency microphonic from the basal turn of the guinea pig cochlea in terms of the three parameters describing this non-linear Boltzmann transfer curve during animal experiments [Patuzzi and Moleirinho, 1998;Patuzzi and O'Beirne, 1999], which allows real-time monitoring of these parameters.…”