Biomedical subjects

C Fåhraeus

Publications and source records attributed to C Fåhraeus.

7 recordsLinked to original sources

PubMed2002

The K-Cl cotransporter in the lobster stretch receptor neurone--a kinetic analysis.

Experiments were performed to define quantitatively the substrate (K(+) and Cl(-)) dependence of the transport function (production of equally large and oppositely directed K(+)and Cl(-) flows/currents) of an earlier (Theander et al., 1999) identified electroneutral K-Cl cotransporter in the slowly adapting stretch receptor neurone of the European lobster. The experiments were based on microelectrode techniques. This allowed us to perform steady-state measurements of the so-called "instantaneous" current-voltage relationships (around a holding voltage of -65 mV after a blockage of the cell's action potential and hyperpolarization-activated currents) and intracellular ion concentrations at various settings of the extracellular K(+) and Cl(-) concentrations. From the results, we could then define steady-state values of all of the cell's non-KCl cotransporter K(+) and Cl(-) currents. Finally, the negative sums of the inferred non-KCl cotransporter K(+) and Cl(-) currents could be taken as equivalents of the K-Cl cotransporter's K(+) and Cl(-) currents for the reason that, in steady state, all membrane currents add up to zero. For the cotransporter currents, thus inferred for a range from 2.5/410.5 to 40.0/448.0 mM external K(+)/Cl(-), we found that their absolute values increased in a nonlinear fashion from about 5 nA cell(-1) at the lowest, to about 20 nA cell(-1) at the highest external K(+)/Cl(-) concentrations. Formally, this relationship could be reproduced by a Hill function-based enzyme kinetic expression simulating inward and outward transmembrane electroneutral ion transports. Following insertion of this expression into a comprehensive model of electrical membrane functions and intracellular solute and solvent control in the lobster stretch receptor neurone, the model predictions suggested that the K-Cl cotransporter does play an important role in (a) keeping intracellular Cl(-) low for a proper function of the cell's inhibitory system, and (b) enabling rapid transmembrane K(+) shifts that provide for a stabilization of the cell's membrane voltage and membrane excitability in cases of varying extracellular K(+) concentrations. The model predictions gave, however, no clear evidence that the K-Cl cotransporter is critically involved in the cell's volume regulation in conditions of varying extracellular osmolalities.

Animals↗

PubMed1999

Cl- transport in the lobster stretch receptor neurone.

Experiments were performed to identify mechanisms underlying non-leakage and non-H+/HCO3--linked transmembrane Cl- transports in the slowly adapting stretch receptor neurone of the European lobster, using intracellular microelectrode and pharmacological techniques. In methodological tests, it was established that direct estimates of intracellular Cl- with ion-sensitive microelectrodes are statistically identical with indirect estimates by means of a GABA method, where 1-2 mM GABA is transforming the cell's membrane voltage into its Cl- equilibrium voltage from which the Cl- concentration is inferred by the Nernst equation. From experiments using sodium orthovanadate and ethacrynic acid, supposed to block primary Cl- pumps, and bumetanide, supposed to block Na-K-Cl co-transporters, it appeared that neither of the two Cl- transport systems exists in the stretch receptor neurone. It could be shown, however, that the cell is equipped with an electroneutral K-Cl co-transporter that (a) is blockable by furosemide in high (Km approximately 350 microM), by 4-acetamido-4'-isothiocyanato-stilbene-2,2-disulphonic acid (SITS) in medium-high (Km approximately 35 microM), and by 4, 4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) in low (Km approximately 15 microM) doses, (b) is (transiently) activatable by (1 mM) n-ethylmaleimide, (c) is not suppressed by extracellular Rb+ or NH4+, and (d) is not directly coupled to any transmembrane transports of Na+, H+ or HCO3-. From functional tests, with varying transmembrane K+ and Cl- gradients, evidence obtained that the K-Cl co-transporter is able to reverse its transport direction and to adjust its transport rate in a considerable range. As a whole, the results speak in favour of the K-Cl co-transporter being responsible (a) for normally keeping the intracellular Cl- concentration at low levels, for an optimization of the cell's inhibitory system, and (b) for achieving fast transmembrane shifts of K+ (and Cl-), as a means of stabilizing the cell's membrane excitability in conditions of varying extracellular K+ concentrations.

Animals↗

PubMed1998

Catch-up primary vaccination with acellular pertussis vaccines in 3-4-year-old children--reactogenicity and serological response.

In order to evaluate the optimum number of doses for catch-up primary vaccination against pertussis, 248 Swedish children 3-4 years of age were randomized to receive either two or three doses of a three-component or a five-component acellular pertussis vaccine. Adverse reactions were mild, but increased with increasing number of doses, especially in a subgroup of 17 children with serological signs of earlier pertussis. There were no clinically significant differences between the two vaccines. Antibody levels against pertussis were higher after two doses in this age group than after three doses in infancy. A primary vaccination program for older children can use two instead of three doses.

Antibodies, Viral↗

PubMed1997

Properties of electrolyte-filled glass microelectrodes: an experimental study.

The electrochemical and electrical properties of geometrically defined electrolyte-filled microelectrodes were studied at various transelectrode current passages, using radiotracer (38Cl and 42K) and electrical techniques. Geometrically, the electrodes were defined by their tip properties that, for standard (single-barrelled, 3.0 M KCl-filled, approximately 10 M[ohm]) electrodes implied a tip opening radius of 0.135 microm and a tip taper of 0.0215 microm/microm in the most distal (0-150 microm), and of 0.0105 microm/microm in the next most distal (150-1000 microm) tip regions. From the radiotracer studies it followed that (a) in the absence of transelectrode current passage, K+ and Cl- are leaking from the electrode tip in amounts corresponding to currents of +/- 3.8 nA, and (b) in the presence of transelectrode current passage, the flow of K+ and Cl- through the electrode tip changes with the transelectrode current in a statistically linear fashion so that K+ carries about 80% and Cl- about 20% of any electrode-injected current. From the electrical measurements it appeared that the standard electrodes are characterized by (a) a tip potential of -2.6 mV, and (b) a resistance that changes from an instantaneous, non-rectifying type to a steady state, outwardly rectifying type, within tenths of a second of constant current flow. The outward current rectification was seen to be reduced by raising [KCl] in the immersing solution, or by lowering it in the filling solution. Together, the observed electrode properties are consistent with the electrode electrolyte's solute and solvent turnover being governed by electro-osmotic as well as by electrodiffusion laws.

Chlorides↗

PubMed1997

Properties of electrolyte-filled glass microelectrodes: a model analysis.

A novel dynamic mathematical microelectrode model (a model of solvent and solute kinetics in electrolyte-filled microelectrodes) was deduced from experimental observations made on standard (single-barrelled, 3.0 M KCl-filled, approximately 10 M[ohm]) electrodes using (a) electrodiffusion, electro-osmosis, and continuity equations that were placed into the constraints of electrode geometry, and (b) handbook/textbook parameter values, only. The model proved to be able to faithfully reproduce all observed electrochemical and electrical electrode properties, i.e. even those that constituted no part of the model's experimental basis. In theoretical tests, the model shows, for the standard electrode that (a) inside the electrode, any profiles in electrical potential and electrolyte concentration are occurring at the most distal part (approximately 50 microm) of the tip region, (b) asymmetrical shifts in electrolyte concentration just inside the electrode tip opening are the true cause of the electrode's current rectification, and (c) strong transelectrode currents are producing water flows across the electrode orifice that may affect the volume of smaller and medium-sized cells. In further tests, the model shows, among other things, for non-standard electrodes that (a) decreasing the electrode electrolyte concentration will give rise to marked decreases in electrolyte leakage from the electrode, but only very minor changes in tip potential, and (b) increasing the surface charge of the electrode glass (increases in zeta potential) and/or decreasing the electrode electrolyte concentration will produce increases in electro-osmotic water transport, which may be desirable for the intracellular injection of water-soluble (electro-neutral) substances.

Electrochemistry↗

PubMed1996

Analysis of leak current properties in the lobster stretch receptor neurone.

Experiments were performed to characterize the so-called leak current of the slowly adapting stretch receptor neurone of the European lobster with respect to its ionic basis, its kinetics and its pharmacology. Estimates of the leak current were obtained by subtraction of a Na-K pump current and of an unspecific impalement current from a non-dynamic ('instantaneous') current, recorded in a voltage range from approximately -120 to approximately -30 mV, after blockage of spike-generating currents and a hyperpolarization-activated inwardly rectifying current (Q-current). The leak current, estimated in this way, was seen to reverse direction at the cell's K+ equilibrium voltage, thus indicating that it is carried by K+ passing through channels which, also, proved to be permeable to Rb+ and NH4+, but not permeable to Na+ or Cl- to any significant extent. Kinetically, the leak current was found to be characterized by being enhanced by increases in extracellular K+ and by being subject to outward rectification, most distinctly at elevated extracellular [K+]. In quantitative terms, these kinetic properties could be accounted for by a mathematical model comprising (1) a one-site two-barrier Eyring formulation describing ion permeation through membrane channels and (2) an ordinary dose-response relationship describing the channel-opening effect of K+ at an extracellular regulatory site. Pharmacologically, the leak current proved to be distinguished by being reversibly blockable, in a non-voltage dependent manner, by CO2+ (Kd = 0.9 mM, Hill coefficient 1.1) and procaine, but not by Ba2+, Gd3+, bupivacaine (a local anesthetic), or other K+ channel blockers such as TEA, 4-AP and Cs+. It is concluded that, in native unimpaled cells, the K+ carried leak current (1) is setting the resting voltage together with the (mainly) Na(+)-carried Q-current and the Na-K pump current, (2) is determining the cell's firing threshold, together with the spike generating currents, and (3) is also stabilizing the cell's membrane excitability in conditions of varying extracellular [K+], by virtue of its K+ sensitivity.

Animals↗

PubMed1989

Small airways function in workers processing polyvinylchloride.

In a polyvinyl chloride (PVC) processing plant, 20 workers employed as machine attendants and calender operators, and thus exposed to PVC thermal degradation products (PTDP) and phthalic acid esters (PAE; up to 2 mg/m3), were studied. The control group was 19 unexposed workers. The exposed subjects had more symptoms from eyes and upper airways than the controls, probably mainly associated with PTDP. Two (10%) exposed workers had mild work-related asthma vs no control; five (25%) vs one (5%) symptoms of unspecific bronchial hyperreactivity. One exposed subject had a significantly raised level of IgG against phthalic anhydride, indicating that sensitization can occur in PVC processing. No significant differences were found between exposed and control subjects with regard to spirometry (VC, FEV1, FEF50, FEF75) or volume of trapped gas (VTG, an indicator of small airways disease) before or after metacholine inhalation. Thus, we could not find effects of PTDP or PAE on the small airways.

Adult↗