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A Strickholm

Publications and source records attributed to A Strickholm.

18 recordsLinked to original sources
PubMed1989

A hybrid patch clamp amplifier.

The current-to-voltage convertor used in patch clamping is analyzed for noise generation and the major noise sources determined. A hybrid patch clamp amplifier design is theoretically analyzed. Here it is shown that by differentiation and recombining of signals the original input signal can be reconstructed. Several circuits of this design are described and their performance compared. The optimal signal detection obtained for a 1 ms current pulse width with a signal-to-noise ratio of 1 is 0.025 pA. In these circuits, high frequency attenuation is readily accomplished with a single control. In addition, compensation for the transients which occur with step control voltages is effectively accomplished. With this circuitry, it is shown that for most patch clamp situations, the minimum pulse width and current which can be detected is determined by the patch clamp seal resistance.

Amplifiers, Electronic↗
PubMed1981

Control of ionic permeability by membrane charged groups: dependency on pH, depolarization, tetrodotoxin and procaine.

The membrane permeabilities of K, Na, and Cl were determined in crayfish giant axons from pH 3.8 to 11.4. In general, cation permeability increases with pH while anion permeability decreases. In normal saline (Ko = 5.4 mM, pH = 7), P(K) = 1.33 X 10-5, P(Cl) - 1.49 X 10-6, and P(Na) = 1.92 X 10-8 cm/s. Increasing external potassium results in a dramatic membrane conductance change around Ko = 12 mM (Vm = -60 mV) which results primarily from changes in P(Na) and P(Cl). In elevated potassium (Ko = 40 mM, pH = 7), P(K), P(Cl), and P(Na) increase by 1.45, 8.1 and 14.2. In the potassium depolarized axon, P(Na) and P(Cl) show a cooperative change when pH is altered through the imidazole pK region (pK = 6.3). These changes are not seen in normal saline, or with P(K). A Hill coefficient n = 4 was found for the cooperative change of P(Na) and P(Cl). An interpretation here is the four protein molecules interact to form the Na and Cl ionic channels. Tetrodotoxin has minimal effects on passive permeabilities but reduce the Hill coefficient n for P(Na) but not P(Cl), while procaine reduces n for both P(Na) and P(Cl). The results show that membrane fixed charged groups have varied association and control over the different ion permeabilities. In addition, membrane conformational changes are also involved in permeability control.

Animals↗
PubMed1979

Drug interactions with nerve membrane components regulating ionic permeability: action of tetrodotoxin, procaine, pentobarbital, and ethanol.

The interaction of neuroactive agents with surface membrane ionizable groups which regulate passive ionic permeability in crayfish giant axons was examined. Every ionizable membrane group was found to contribute in various degrees to regulating membranes ionic permeability. However, some membrane ionizable groups have dominant control over specific ions. Thus potassium and sodium passive permeability is predominantly activated by deprotonation of imidazole on protein and the secondary ionization of phosphatidic acid. Chloride permeability appears activated almost entirely by protonation of amino side groups on protein. The conformational state of membrane protein which regulates ionic permeability changed when the axon was potassium depolarized. The effects of tetrodotoxin, ethanol, and the amphipathic molecules procaine and pentobarbital, on the passive ionic conductances were determined. Both procaine and pentobarbital could, when charged, alter specific ionic conductances through their effects on surface double layer potentials although protein conformational changes were also involved. Studies on animals made dependent with ethanol showed an increased passive sodium conductance which further increased following ethanol withdrawal. A physical mechanism for ethanol dependency is suggested. Although the above four agents show differences in how they alter specific ionic conductances of nerve, their common mode of action, at concentrations which block the action potential, is to prevent a normal conformational change in membrane protein from occurring when nerve is depolarized.

Animals↗
PubMed1978

Oxidized cholesterol bilayers. Dependence of electrical properties on degree of oxidation and aging.

Black lipid membranes made from oxidized cholesterol were examined for their specific resistance, capacitance, and physical stability, as a function of cholesterol oxidation time and of age. Membranes formed from cholesterol oxidized in n-octane were not physically stable even after 7 h of oxidation unless they were aged for at least a month. Membranes formed from cholesterol oxidized in decane and tetradecane (1 : 1) were stable immediately after 2--6 h of oxidation. Oxidation times outside this range produced unstable membranes. After 1 month storage, membranes from cholesterol solutions oxidized in decane and tetradecane from 0.75--3 h were stable. After 11 months, only the 0.75 oxidation time produced stable membranes. Storage in nitrogen retarded the aging process. After initial forming of the membrane, total membrane area and capacity increased and then stabilized, although specific capacity and resistance did not change, indicating inherent stability in the bilayer's intrinsic electrical properties. Bilayers formed soon after cholesterol oxidation had membrane capacity which ranged from 0.42 to 0.55 muF/cm2. Specific membrane resistance ranged initially from 2 . 10(6) to 37 . 10(6) omega/cm2 in 0.2 M NaCl with lower resistances in the more oxidized membranes. With aging, membrane capacity decreased gradually over 11 months to values approaching 0.1 muF/cm2 indicating membrane thickening. Membrane resistance ordinarily decreases with storage time. The rate of these changes with age is dependent on the extent of initial cholesterol oxidation and subsequent oxidation, with long term stability best in the least oxidized membranes.

Cholesterol↗
PubMed1977

Ionic permeability of K, Na, and Cl in crayfish nerve. Regulation by membrane fixed charges and pH.

Teorell's fixed charge theory for membrane ion permeability was utilized to calculate specific ionic permeabilities from measurements of membrane potential, conductance, and specific ionic transference numbers. The results were compared with the passive ionic conductances calculated from the branched equivalent circuit membrane model of Hodgkin Huxley. Ionic permeabilities for potassium, sodium, and chloride of crayfish (Procambarus clarkii) medial giant axons were examined over an external pH range from 3.8 to 11.4. Action potentials were obtained over this pH range. Failures occurred below pH 3.8 during protonation of membrane phospholipid phosphate and carboxyl, and above pH 11.4 from calcium precipitation. In general, chloride permeability increases with membrane protonation, while cation permeability decreases. At pH 7.0, PK = 1.33 X 10(-5), PCl = 1.49 X 10(-6), PNa = 1.92 X 10(-8) cm/s. PK: PCl: PNa = 693:78:1. PCl is zero above pH 10.6 and is opened predominately by protonation of epsilon-amino, and partially by tyrosine and sulfhydryl groups from pH 10.6 to 9. PK is activated in part by ionization of phospholipid phosphate and carboxyl around pH 4, then further by imidazole from pH 5 to 7, and then predominately from pH 7 to 9 by most probably phosphatidic acid. PNa permeability parallels that of potassium from pH 5 to 9.4. Below pH 5 and above pH 9.4, PNa increases while PK decreases. Evidence was obtained that these ions possibly share common passive permeable channels. The data best support the theory of Teorell, that membrane fixed charges regulate permiability and that essentially every membrane ionizable group appears involved in various amounts in ionic permeability control.

Action Potentials↗
PubMed1969

The pH dependency of relative ion permeabilities in the crayfish giant axon.

The dependence of the membrane potential on potassium, chloride, and sodium ions, was determined at the pH's of 6.0, 7.5, and 9.0 for the resting and depolarized crayfish ventral nerve cord giant axon. In normal saline (external potassium = 5.4 mM), the dependence of the membrane potential on the external potassium ions decreased with lowered pH while that for chloride increased. In contrast, in the potassium depolarized axon (external potassium = 25 mM), the dependence of the membrane potential on external potassium was minimum around pH 7.5 and increased in either more acidic or basic pH. In addition, the dependence of the membrane potential on external chloride in the depolarized axon was maximum at pH 7.5 and decreased in either more acidic or basic pH. The sodium dependency of the membrane potential was small and relatively unaffected by pH or depolarization. The data are interpreted as indicating a reversible surface membrane protein-phospholipid conformation change which occurs in the transition from the resting to the depolarized axon.

Animals↗
PubMed1967

Relative ion permeabilities in the crayfish giant axon determined from rapid external ion changes.

The changes in membrane potential of isolated, single crayfish giant axons following rapid shifts in external ion concentrations have been studied. At normal resting potential the immediate change in membrane potential after a variation in external potassium concentration is quite marked compared to the effect of an equivalent chloride change. If the membrane is depolarized by a maintained potassium elevation, the immediate potential change due to a chloride variation becomes comparable to that of an equivalent potassium change. There is no appreciable effect on membrane potential when external sodium is varied, at normal or at a depolarized membrane potential. Starting from the constant field equation, expressions for the permeability ratios P(Cl)/P(K), P(Na)/P(K), and for intracellular potassium and chloride concentrations are derived. At normal resting membrane potential, P(Cl)/P(K) is 0.13 but at a membrane potential of -53 mv (external potassium level increased about five times) it is 0.85. The intracellular concentrations of potassium and chloride are estimated to be 233 and 34 mM, respectively, and it is pointed out that this is not compatible with ions distributed in a Nernst equilibrium across the membrane. It is also stressed that the information given by a plot of membrane potential vs. the logarithm of external potassium concentrations is very limited and rests upon several important assumptions.

Animals↗