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Biomedical subjects

I C Forster

Publications and source records attributed to I C Forster.

32 records · Page 2Linked to original sources

Kinetic analysis of the sodium gating current in the squid giant axon.

A critical study has been made of the characteristics of the kinetic components of the sodium gating current in the squid giant axon, of which not less than five can be resolved. In addition to the principal fast component Ig2, there are two components of appreciable size that relax at an intermediate rate, Ig3 alpha and Ig 3 beta. Ig3 alpha has a fast rise, and is present over the whole range of negative test potentials. Ig3 beta is absent below -40 mV, exhibits a delayed onset and disappears on inactivation of the sodium system. There are also two smaller components, Ig1 and Ig4, with very fast and much slower relaxation time constants, respectively.

Animals↗

High resolution recording of asymmetry currents from the squid giant axon: technical aspects of voltage clamp design.

The design, realisation and performance of a voltage clamp system dedicated to recording asymmetry currents from the squid giant axon is presented. The design has been optimised with respect to dynamic response, signal-to-noise ratio and linearity. Analytical expressions are given for both the dynamic performance and noise characteristics which simplify the design and setting up of the clamp and provide excellent agreement between design theory and practice. A 0.5 cm2 area of membrane can be voltage clamped in response to a command input voltage step within 10 microseconds with smooth settling and up to 100% of the effective series resistance being compensated. The noise contributions of the recording chamber, voltage sensing electrodes and clamp electronics have been reduced such that recording of gating currents with a more than 10-fold reduction in the number of averages required compared with previous clamp designs is possible. The overall system nonlinearity results in typically less than 1% contribution to the measured asymmetry charge.

Animals↗

Gating current associated with inactivated states of the squid axon gating channel.

Sodium (Na) channel gating currents were measured in squid (Loligo forbesi) axons to study transitions among states occupied by the Na channel when it is inactivated. These measurements were made at high temporal resolution with a low-noise voltage clamp. The inactivation-resistant gating current, I(g,inact), could be separated into a very fast (tau = 5-25 mus) and a slower (tau = 40-200 mus) component over a wide range of test potentials (-140 mV to 80 mV) and for three different starting potentials (-70 mV, 0 mV, and 50 mV). The time constants for these components plotted against test potential lay on two bell-shaped curves; the time constants at any particular test potential did not depend on the starting potential. Both components had charge-voltage curves that saturated between -150 mV and 50 mV. A fast spike, similar to the fast component of I(g, inact), was also apparent in recordings of the fully recovered total "on" gating current. I(g, inact)(fast) and I(g, inact)(slow) could not together be described by the simplest possible model, a linear three-state scheme; however, I(g, inact)(fast) could be modeled by a two-state scheme operating in parallel with other gating processes. I(g, inact)(slow) and the gating current due to recovery from inactivated states into resting states could together be well described by a three-state scheme. This lends support to models in which a pair of inactivated states are connected by a single voltage-dependent step to the resting states of the Na system.

Animals↗

Single-channel current simulation and recording using a photodiode as current generator.

A device which can generate rectangular currents in the picoampere range is described. The current generator is a photodiode connected to the head stage of a single-channel recording amplifier. The photodiode is activated by a light-emitting diode controlled by a computer or any other current source. The device can transmit signals corresponding to simulated single-channel behaviour. Since the kinetic parameters of the simulation are known, the user can test the data acquisition and analysis system under conditions similar to those prevailing during recording from a biological membrane. This current generator can also be used for the tuning of patch-clamp amplifiers; rectangular currents generated by the photodiode allow the frequency response of the amplifier to be properly adjusted.

Electric Stimulation↗

Technical aspects of voltage-clamping the cut-open squid giant axon.

The design of a voltage-clamp system dedicated to recording the fluctuation of sodium currents under non-stationary conditions from a leaflet of cut-open squid axon is presented. The membrane leaflet is mechanically sandwiched between the apices of two finely machined plexiglass cones which enable fluid access to each side of the membrane and a known area of membrane to be voltage-clamped. The design requirements necessary to achieve satisfactory signal resolution have been assessed in terms of the overall digitising resolution of the ADC hardware and the intrinsic and extrinsic components of the clamp-system noise. Good agreement between the predicted and measured noise performance was found. The clamp system has enabled simultaneous estimates of the single-channel conductance and channel density to be made over a much wider range of experimental conditions than previously possible.

Animals↗

Data recording and playback on video tape--a multi-channel analog interface for a digital audio processor system.

The design of an analog interface to a digital audio signal processor (DASP)-video cassette recorder (VCR) system is described. The complete system represents a low-cost alternative to both FM instrumentation tape recorders and multi-channel chart recorders. The interface or DASP input-output unit described in this paper enables the recording and playback of up to 12 analog channels with a maximum of 12 bit resolution and a bandwidth of 2 kHz per channel. Internal control and timing in the recording component of the interface is performed using ROMs which can be reprogrammed to suit different analog-to-digital converter hardware. Improvement in the bandwidth specifications is possible by connecting channels in parallel. A parallel 16 bit data output port is provided for direct transfer of the digitized data to a computer.

Electrocardiography↗

Theoretical design and implementation of a transcutaneous, multichannel stimulator for neural prosthesis applications.

The development of a transcutaneous, implantable, multichannel neural stimulator is described. This was originally dedicated to the stimulation of the auditory nerve in profoundly deaf persons, but is sufficiently flexible in design and operation to be applicable to other areas of neural prosthetics. Control of both the amplitude and time of stimulation for up to fifteen independent channels is possible with a maximum stimulation rate of 1 kHz. Particular attention is given to the design of the transcutaneous link stage which allows both power and data to be transferred to the implanted device using a compact coupling inductor configuration. All circuit timing is derived from a single clock in the external transmitter unit, resulting in stable operation with predictable stimulus output characteristics. The implantable device, realised using thick film hybrid techniques, employs CMOS logic extensively to reduce power consumption. One such device has been implanted in a profoundly deaf volunteer for a period exceeding two years and has continued to operate reliably in conjunction with the complete prosthesis system.

Cochlear Implants↗

A multiple-electrode hearing prosthesis for cochlea implantation in deaf patients.

A multiple-electrode hearing prosthesis for cochlea implantation in deaf patients has been developed at the University of Melbourne. It has been designed as a multiple-electrode implant to provide the best chance of enabling patients to understand speech. It has been shown that an electrode array can be threaded along the coills of the inner ear close to residual auditory nerves. Experimental studies have indicated that the long-term implantation of the array will not lead to significant degeneration of auditory nerve fibres. Loss of platinum from the stimulating electrodes can be minimized with a biphasic constant current pulse, where the first phase is negative with respect to ground. The receiver-stimulator component has also been designed to provide 10-15 channels of stimulation. Furthermore, the phase and amplitude of the stimuli to individual electrodes can be varied to enable the localization of the electrical fields to discrete groups of nerve fibres, and the correct method of frequency and intensity coding to be determined. Finally, the device should be used in the first instance for a specially selected group of adults who are post-lingually deaf.

Animals↗

A multiple electrode cochlear implant.

The University of Melbourne Departments of Otolaryngology and Electrical Engineering (UMDOLEE) receiving and stimulating component of a multiple-electrode cochlear implant hearing prosthesis produces constant stimulation. It has a stimulating pulse shape that minimizes the production of toxic substances and loss of metal from the electrodes, and this is achieved with a biphasic rectangular waveform where the first phase is negative with respect to ground. The duration of each stimulus phase in 180 msec, which is long enough to allow low levels of current stimulation, and short enough to permit rates of 1000 pulses/second to be achieved. In order to be consistent with our present understanding of the perception of pitch, the device permits the independent stimulation of a number of electrodes. Furthermore, to electrically isolate the stimulus to small areas, there is the capacity to vary the current and set the threshold independently at individual electrodes. The phase and amplitude of the pulses to neighbouring electrodes with also be varied to assist in localizing the current flow. The pattern to stimulation to individual or groups of electrodes can also be altered to enable studies to be carried out to determine ways of conveying frequency and intensity information over a more normal dynamic range.

Animals↗

Molecular characteristics of phosphate transporters and their regulation.

A key process in overall P(i)-homeostasis is renal proximal tubular reabsorption of inorganic phosphate (P(i)), which involves secondary active sodium/phosphate (Na(+)/P(i)) cotransport reabsorption at the brush border membrane. Among the two different molecularly identified Na(+)/P(i) cotransporters, the type-IIa Na(+)/P(i) cotransporter (NaPi-IIa) accounts for up to 70% of brush border membrane transport. Regulation of renal P(i) reabsorption centers around brush border membrane insertion and retrieval of transporter protein under the influence of hormonal and nonhormonal factors. Immunohistochemical and fluorescence techniques have provided new insights into the tissue distribution and the regulation processes. The intrinsic electrogenicity of NaPi-IIa, has allowed detailed studies of the transport kinetics of NaPi-IIa and, combined with mutagenesis methods, structure-function information at the protein level is emerging.

Amino Acid Sequence↗