Biomedical subjects

S Draber

Publications and source records attributed to S Draber.

6 recordsLinked to original sources

PubMed1994

Fast single-channel measurements resolve the blocking effect of Cs+ on the K+ channel.

The Cs+ block of K+ channels has often been investigated by methods that allow only indirect estimation of the rate constants of blocking and re-opening. This paper presents single-channel records with high temporal resolution which make the direct observation of the fast transitions between the blocked and the unblocked state possible. The rate constants kOGb, kGbO of Cs(+)-dependent blocking and of re-opening are evaluated from the time constants found in the open-time and closed-time histograms. The blocking rate constant kOGb between 1000 and 50000 s-1 depends linearly on the Cs+ concentration and strongly on voltage, increasing by a factor of 1.44 per 10 mV hyperpolarization. The re-opening rate constant kGbO approximately 30000 s-1 is independent of Cs+ concentration and only slightly voltage-dependent. Formally, the results can be described by a Woodhull-model. The strong voltage dependence with d > 1, however, weakens its plausibility. The results are interpreted in terms of a molecular framework emerging from recent results on the structure of voltage-gated channels.

Cesium↗

PubMed1994

Detection of jumps in single-channel data containing subconductance levels.

Detection algorithms are widely used for the analysis of single-channel data because they remove the background noise from the measured current signal and reconstruct the noise-free time series. Standard detection algorithms assume channels switching only between zero and full conductance. Many types of channels, however, show subconductance levels. A new detection algorithm for data containing sublevels, the so-called sublevel Hinkley-detector (SHD), calculates several test values in parallel, one for each possible jump. The velocity of increase has a maximum for the correct jump. This feature is used to detect the jump and to diagnose the new level of current. Because patch-clamp data are always filtered by an antialiasing low-pass filter before sampling, the algorithm is supplemented by a special diagnosis phase accounting for the distortion of the originally rectangular jumps. Along with the reconstructed (noise-free) time series the SHD also gives a matrix of the transition counts between the levels. This matrix is a useful statistical tool for the decision whether the observed channel(s) have in fact a subconductance conformation or if there are simply several channels of different conductivity contained within the patch.

Algorithms↗

PubMed1994

Correction for missed events based on a realistic model of a detector.

Quantitative patch-clamp analysis based on dwell-time histograms has to deal with the problem of missed events. The correction of the evaluated time constants has to take into account the characteristics of the detector used for the reconstruction of the time series. In previous approaches a simple model of the detector has been used, which is based on the assumption that all events shorter than the temporal resolution tres were missed, irrespective of the preceding events. Rather than the standard assumption of a fixed dead time, we introduce a more realistic model of a detector by a continuous-time version of the Hinkley detector. The combined state of the channel and the detector obeys a Markov model, which is governed by a Fokker-Planck-Kolmogorov partial differential equation. The steady-state solution leads to the determination of the apparent time constants tau o and tau c depending on the true rate constants koc and kco and the temporal resolution tres of the detector. Simulations with different kinds of detectors, including the Bessel filter with half-amplitude threshold detection, are performed. They show that our new equation predicts the dependence of tau c and tau o on koc, kco, and tres better than the standard equation used until now.

Ion Channel Gating↗

PubMed1993

A nonlinear filter algorithm for the detection of jumps in patch-clamp data.

This paper presents a new algorithm for the detection of channel openings and closures from noisy current signals, especially for the correct generation and interpretation of open-time and closed-time histograms. The Hinkley detector is a nonlinear off-line jump detection algorithm from the field of fault detection. Here, an improved version, the higher-order Hinkley detector H.O.H.D., is developed. A general description of the sensitivity of a detector is introduced by the time resolution tres. This allows a comparison of the nonlinear detectors with the standard threshold detectors preceded by a low-pass filter for noise suppression. By means of application to simulated and real data, the performance of the detection algorithms is investigated. The higher-order Hinkley detector gave the best results with respect to correct reconstruction of the event length, to a small amount of missed brief events as well as to the ability to achieve short time resolution without pretending false events, especially in the presence of colored noise.

Algorithms↗

PubMed1993

Cooperative behavior of K+ channels in the tonoplast of Chara corallina.

Spontaneous cooperatively of K+ channels is studied in excised patches of Chara corallina tonoplasts. Bar histograms (dwell time versus number of open channels) are constructed from the time series of current by means of the higher-order Hinkley detector (R. Schultze and S. Draber. 1993. J. Membr. Biol. 132:41-52). A statistical test, based on these bar histograms, shows that the channels are not independent. Further analysis reveals that the channels are cooperatively changing their open probability, which leads to the idea of cooperative mode shifting.

Biophysical Phenomena↗

PubMed1991

Patch-clamp studies on the anomalous mole fraction effect of the K+ channel in cytoplasmic droplets of Nitella: an attempt to distinguish between a multi-ion single-file pore and an enzyme kinetic model with lazy state.

Patch-clamp studies have been employed in order to check whether the assumption of a multi-ion single-file pore is necessary for the explanation of the anomalous mole fraction effect or whether this effect can also be explained by a single-barrier enzyme kinetic model. Experiments in the cell-attached configuration were done on the tonoplast membrane of cytoplasmic droplets of Nitella in solutions containing 150 mol m-3 of K+ plus Tl+ with seven different K+/Tl+ ratios. At first sight, the results seem to support the multi-ion single-file pore, because apparent open channel conductivity displays the anomalous mole fraction effect, whereas open-probability has not been found to be dependent on the K+/Tl+ ratio. Changes in open probability would be expected for a single-barrier enzyme kinetic model with a lazy state. On the other hand, the lazy-state model is more successful in explaining the measured I-V curves. The entire slope of the apparent open channel current-voltage curves rotates with changing K+/Tl+ ratios in the whole voltage range between -100 and +80 mV. Numerical calculations on the basis of multi-ion single-file pores could create the anomalous mole fraction effect only in a limited voltage range with intersecting I-V curves. The apparent absence of an effect on open probability which is postulated by the lazy-state model can be explained if switching into and out of the lazy state is faster than can be resolved by the temporal resolution of 1 msec.

Biological Transport↗