PubMed Health⌕ Search

Biomedical subjects

C L Schauf

Publications and source records attributed to C L Schauf.

At least 19 recordsLinked to original sources
PubMed1990

Fractal filtering of channel data.

The fractal dimension of subsets of time series data can be used to modulate the extent of filtering to which the data is subjected. In general, such fractal filtering makes it possible to retain large transient shifts in baseline with very little decrease in amplitude, while the baseline noise itself is markedly reduced (Strahle, W.C. (1988) Electron. Lett. 24, 1248-1249). The fractal filter concept is readily applicable to single channel data in which there are numerous opening/closing events and flickering. Using a simple recursive filter of the form: Yn = w.Yn-1 + (1 - w)Xn, where Xn is the data, Yn the filtered result, and w is a weighting factor, 0 less than w less than 1, we adjusted w as a function of the fractal dimension (D) for data subsets. Linear and ogive functions of D were used to modify w. Of these, the ogive function: w = [1 + p(1.5-D)]-1 (where p affects the amount of filtering), is most useful for removing extraneous noise while retaining opening/closing events.

Calcium↗
PubMed1987

Zonisamide enhances slow sodium inactivation in Myxicola.

In voltage-clamped Myxicola giant axons Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) caused a hyperpolarizing shift in the steady-state fast inactivation curve and retarded recovery from fast and slow Na+ inactivation. The effects of Zonisamide on steady-state fast inactivation could be described assuming a single binding site with a dissociation constant of 12 microM. Slow inactivation was significantly more sensitive, with a Kd of 1 microM from both steady-state and kinetic data. While these results account for anticonvulsant activity, the differential sensitivity suggests Zonisamide may also be useful in studies of the slow inactive state of the Na+ channel.

Animals↗
PubMed1987

Effects of abscisic acid on K+ channels in Vicia faba guard cell protoplasts.

Potassium channels were resolved in Vicia faba guard cell protoplasts by patch voltage-clamp. Whole-cell currents and single K+ channels had linear instantaneous current-voltage relations, reversing at the calculated Nernst potential for K+. Whole cell K+ currents activated exponentially during step depolarizations, with half-activation times of 400-450 msec at +80 mV and 90-110 msec at +150 mV. Single K+ channel conductance was 65 +/- 5 pS with a mean open time of 1.25 +/- 0.30 msec at 150 mV. Potassium channels were blocked by internal Cs+ and by external TEA+, but they were insensitive to external 4-aminopyridine. Application of 10 microM abscisic acid increased mean open time and caused long-lasting bursts of channel openings. Since internal and external composition can be controlled, patch-clamped protoplasts are ideal systems for studying the role of ion channels in plant physiology.

Abscisic Acid↗
PubMed1987

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA.

Voltage-dependent K+ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K+ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K+ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K+ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K+ channels in frog nerves depends on fiber diameter. The size dependence was used to determine the relative sensitivity of nodal and internodal K+ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K+ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K+ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.

4-Aminopyridine↗
PubMed1987

Selective modification of sodium channel gating by solvents and drugs.

In Myxicola heavy water (D2O) does not alter Na+ gating currents, but slows activation and inactivation. In this study, the solvent formamide (5-20% v/v) is shown to proportionately and reversibly block Na+ currents and charge movement, suggesting it may be useful for fractionating gating currents. Formamide- and prepulse-sensitive (inactivating) gating currents were identical, comprising 60-80% of total charge. Both had rising phases and decayed as single exponential functions. Formamide-insensitive and non-inactivating charge movements had no rising phases and decayed slowly with more complex kinetics. Another solvent, dimethylsulfoxide (1% v/v), had no effect on Na+ activation or charge movement, though it did affect inactivation. Amantadine (0.1 mM) did not change Na+ activation or charge movement, but slowed inactivation and shifted the foot of the steady state Na+ inactivation curve. Sotalol (0.1 mM) slowed inactivation, but also inhibited Na+ activation and gating current.

Amantadine↗
PubMed1987

Membrane-directed effects of the plant hormones abscisic acid, indole-3-acetic acid and 2,4-dichlorophenoxyacetic acid.

This study examines two ways plant hormones might influence membrane processes, effects on overall permeability and modifications of specific ion channels. Abscisic acid (ABA) and indole-3-acetic acid (IAA) greatly enhanced erythritol permeability in mixed egg lecithin bilayers. In single component dioleoylphosphatidylcholine bilayers ABA was less effective than IAA, while 2,4-dichlorophenoxyacetate (2,4-D) did not affect either system or alter their ABA response. In Myxicola axons ABA and IAA had no effect, while 2,4-D (10 uM) caused a depolarizing shift of voltage-dependent Na+ and K+ activation by 25 +/- 4 mV and 15 +/- 3 mV, consistent with internal negative surface charge changes of -0.002 e-/A2 and -0.0007 e-/A2. We conclude that both generalized and ion channel-directed effects may link plant hormones and intracellular regulation.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1987

Selective blockade of components of potassium activation in Myxicola axons.

The K+ conductance in Myxicola giant axons activates in two phases which are pharmacologically separable. The fast phase of K+ activation is specifically inhibited by 4-aminopyridine and by the substitution of D2O for H2O. We suggest Myxicola giant axons, like the amphibian node of Ranvier, may possess more than one variety of K+ channel.

4-Aminopyridine↗
PubMed1987

4-Aminopyridine improves clinical signs in multiple sclerosis.

Twelve temperature-sensitive male patients with multiple sclerosis and 5 normal men were monitored before, during, and after the intravenous injection of 7 to 35 mg of 4-aminopyridine (4-AP) in 1- to 5-mg doses, every 10 to 60 minutes. Static quantitative perimetry, flicker-fusion frequency, visual acuity, and videotaped neurological examinations were performed. Ten of the 12 patients showed mild to marked improvement. Vision improved in 7 patients, oculomotor function in 5, and motor function (power, coordination, gait) in 5. Improvements developed gradually within minutes of drug injection at doses as low as 2 mg, and gradually reversed around 2 to 4 hours after the peak drug effect. No effects were observed in 5 patients given saline injections. No serious side effects occurred in either the normal subjects or the patients receiving 4-AP. It is concluded that 4-AP lessens multiple neurological deficits in multiple sclerosis and, furthermore, that the K+ channel is functional in demyelinated central nervous system axons in humans. The improvements with 4-AP are substantial enough to be of transient therapeutic benefit in selected patients.

4-Aminopyridine↗
PubMed1987

Properties of single Na+ channels in cut-open Myxicola giant axons.

Time- and voltage-dependent behavior of the Na+ conductance in dialyzed intact Myxicola axons was compared with cut-open axons subjected to loose-patch clamp of the interior and to axons where Gigaseals were formed after brief enzyme digestion. Voltage and time dependence of activation, inactivation, and reactivation were identical in whole-axons and loose-patch preparations. Single channels observed in patch-clamp axons had a conductance of 18.3 +/- 2.3 pS and a mean open time of 0.84 +/- 0.12 ms. The time-dependence of Na+ currents found by averaging patch-clamp records was similar to intact axons, as was the voltage dependence of activation. Steady-state inactivation in patch-clamped axons was shifted by an average of 15 mV from that seen in loose-patch or intact axons. Substitution of D2O for H2O decreased single channel conductance by 24 +/- 6% in patch-clamped axons compared with 28 +/- 4% in intact axons, slowed inactivation by 58 +/- 8% compared with 49 +/- 6%, and increased mean open time by 52 +/- 7%. The results confirm observations on macroscopic channel behavior in Myxicola and resemble that seen in other excitable tissues.

Animals↗
PubMed1987

Anticonvulsants modify inactivation but not activation processes of sodium channels in Myxicola axons.

The effects of pronase and the anticonvulsant drugs diphenylhydantoin, bepridil, and sodium valproate on fast and slow Na+ inactivation were examined in cut-open Myxicola giant axons with loose patch-clamp electrodes applied to the internal surface. Pronase completely eliminated fast Na+ inactivation without affecting the kinetics of Na+ activation or the maximum Na+ conductance. The time and voltage dependences of slow inactivation following pronase treatment were identical to those measured before enzyme application in the same axons. All three anticonvulsants slowed the time course of recovery from fast Na+ inactivation in untreated axons, and shifted the steady-state fast inactivation curve in the hyperpolarizing direction along the voltage axis. Anticonvulsants enhanced steady-state slow inactivation and retarded recovery from slow inactivation in both untreated and pronase-treated axons. Although some quantitative differences were seen, the order of potency of the anticonvulsants on slow Na+ inactivation was the same as that for recovery from fast inactivation.

Animals↗
PubMed1987

Dendrotoxin blocks potassium channels and slows sodium inactivation in Myxicola giant axons.

Dendrotoxin (DTX) is known to partially block delayed rectifier K+ channels and enhance neurotransmitter release, but no effects on Na+ channels have been reported. In voltage-clamped Myxicola axons DTX affected both the K+ and Na+ conductances. DTX blocked completely Myxicola K+ channels with a KD of 150 nM and induced slow K+ inactivation. DTX doubled the time constants for inactivation of conducting Na+ channels and gating charge immobilization without altering Na+ activation or the voltage- and time-dependent fast and slow Na+ inactivation induced by depolarizing prepulses. A selective effect on open Na+ channel inactivation provides additional evidence for kinetic models in which resting Na+ channels need not open before being inactivated.

Animals↗
PubMed1987

Tetrahydroaminoacridine blocks potassium channels and inhibits sodium inactivation in Myxicola.

In voltage-clamped Myxicola giant axons internally and externally applied tetrahydroaminoacridine (THA) blocked K+ channels with a dissociation constant of 100 microM and slowed their rate of activation. At a concentration of 10 microM, internal THA primarily slowed inactivation of conducting Na+ channels. At 100 microM the decline of the Na+ current during depolarizing pulses was biphasic, with an initial phase 2 to 3 times faster than in control axons. In the presence of THA there was a steady-state inward current accompanied by an increase in amplitude and time constant of Na+ tail currents, as if THA blocked Na+ channels by first entering them and then rendered THA-occluded channels resistant to fast inactivation. THA did not alter activation, prepulse-induced fast inactivation or slow inactivation. The effects of THA on voltage-dependent axonal ion channels might account for central nervous system hyperexcitability seen in some patients treated with THA. Because THA is a potent, centrally active anticholinesterase, even subtle ion channel-directed effects might contribute to its putative antidementia action in clinical states involving a central nervous system deficiency of acetylcholine by selective augmentation of acetylcholine release and/or negation of autoreceptor effects of endogeneous acetylcholine.

Acetylcholine↗
PubMed1979

Modifications of sodium channel gating in Myxicola giant axons by deuterium oxide, temperature, and internal cations.

In dialyzed Myxicola axons substitution of heavy water (D2O) externally and internally slows both sodium and potassium kinetics and decreases the maximum conductances. Furthermore, this effect is strongly temperature dependent, the magnitude of the slowing produced by D2O substitution decreasing with increasing temperature over the range 3-14 degrees C with a Q10 of approximately 0.71. The relatively small magnitude of the D2O effect, combined with its strong temperature dependence, suggests that the rate limiting process producing a conducting channel involves appreciable local changes in solvent structure. Maximum conductances in the presence of D2O were decreased by approximately 30%, while the voltage dependences of both gNa and gK were not appreciably changed. In contrast to the effects of heavy water substitution on the ionic currents, membrane asymmetry currents were not altered by D2O, suggesting that gating charge movement may preceed by several steps the final transformation of the Na+ channel to a conducting state. In Myxicola axons the effect of temperature alone on asymmetry current kinetics can be well described via a simple temporal expansion equivalent to a Q10 of 2.2, which is somewhat less than the Q10 of GNa activation. The integral of membrane asymmetry current, representing maximum charge movement, is however not appreciably altered by temperature.

Animals↗
PubMed1979

Immobilization of intramembrane charge in Myxicola giant axons.

1. Immobilization of gating charge was examined in Myxicola giant axons dialysed with Cs+. 2. With increasing pulse durations the ratio QOFF/QON decreases to as little as 0.25 with a time constant of 3.2 msec determined from composite data. Na inactivation time constants measured in the same axons ranged from 0.8 to 1.5 msec. A slow component of QOFF tends to appear as QOFF/QON decreases. 3. Both QON and QOFF may be decreased by a prepulse with no change in their time course. In this case the time course of the decrease is similar to that observed for INA. 4. The normalized steady-state charge immobilization curve is shifted in the depolarized direction by 15--20 mV from the normalized Na inactivation curve.

Animals↗
PubMed1978

Internal cesium alters sodium inactivation in Myxicola.

When Myxicola giant axons are internally dialyzed with Cs+ as the sole cation, the time-course of prepulse inactivation is selectively accelerated compared to its rate with K+ dialysis in the same axons. This decrease in tauph occurs without any change in the magnitude or time-course of INa during step depolarizations and results in tauph/taush ratios near unity over most of the potential range in Cs+ dialyzed axons.

Animals↗
PubMed1978

Combined voltage-clamp and dialysis of Myxicola axons: behaviour of membrane asymmetry currents.

4. A new technique for the simultaneous internal dialysis and voltage-clamp of Myxicola axons is described and shown to control the internal composition of the axon adequately. 2. The permeability ratio (PNa/PK) of the sodium channel is 15.5 in axons dialysed with sodium-free solutions, somewhat higher than observed in perfused axons. 3. Asymmetry currents are easily recorded in dialysed Myxicola axons. At 4--5 degrees C for pulse durations sufficiently short Qon = Qoff with a maximum charge displacement of 10 nC/cm2 and half the charge being displaced by a step to -32 mV. Maximum slope of the Q(V) curve is 15 mV/e-fold change in charge displaced. The time constant tau on reaches a maximum of 325 microseconds at a potential of -23 mV. 4. The time course of sodium activation cannot be adequately accounted for by (Q/Q infinity) X using any single value of X for potentials between -40 and 40 MV. 5. Both asymmetry currents and INa are inactivated by the same amount when Myxicola axons are repetitively depolarized at frequencies from 0.1 to 50 Hz.

Animals↗