Biomedical subjects

A Wenning

Publications and source records attributed to A Wenning.

8 recordsLinked to original sources

PubMed2001

Indirectly gated Cl(-)-dependent Cl(-) channels sense physiological changes of extracellular chloride in the leech.

The maintenance of ion homeostasis requires adequate ion sensors. In leeches, 34 nephridial nerve cells (NNCs) monitor the Cl(-) concentration of the blood. After a blood meal, the Cl(-) concentration of leech blood triples and is gradually restored to its normal value within 48 h after feeding. As previously shown in voltage-clamp experiments, the Cl(-) sensitivity of the NNCs relies on a persistent depolarizing Cl(-) current that is turned off by an increase of the extracellular Cl(-) concentration. The activation of this Cl(-)-dependent Cl(-) current is independent of voltage and of extra- and intracellular Ca(2+). The transduction mechanism is now characterized on the single-channel level. The NNC's sensitivity to Cl(-) is mediated by a slowly gating Cl(-)-dependent Cl(-) channel with a mean conductance of 50 pS in the cell-attached configuration. Gating of the Cl(-) channel is independent of voltage, and channel activity is independent of extra- and intracellular Ca(2+). Channel activity and the macroscopic current are reversibly blocked by bumetanide. In outside-out patches, changes of the extracellular Cl(-) concentration do not affect channel activity, indicating that channel gating is not via direct interaction of extracellular Cl(-) with the channel. As shown by recordings in the cell-attached configuration, the activity of the channels under the patch is instead governed by the Cl(-) concentration sensed by the rest of the cell. We postulate a membrane-bound Cl(-)-sensing receptor, which-on the increase of the extracellular Cl(-) concentration-closes the Cl(-) channel via a yet unidentified signaling pathway.

Animals↗

PubMed1999

Sensing effectors make sense.

'Housekeepers' of living organisms maintain salt and water balance, monitor blood sugar and schedule their work to the season and the time of day. In order to perform their chores, they rely on information about the status quo. The traditional concept of a sensor that communicates with a central comparator authorizing an effector, which was inspired by engineers, has become blurred in the search for morphological correlates of such regulatory cascades. In many cases, neurones, which are both sensory and neurosecretory, and endocrine cells equipped with smart detectors, reliably regulate autonomous functions by using local rather than central computing. Like the well-trained staff of a smoothly run household, such 'sensing effectors' translate information into action.

Animals↗

PubMed1997

Chloride secretion drives urine formation in leech nephridia.

The transport mechanisms underlying urine formation in leech nephridia were investigated in situ and in isolated preparations using pharmacological, electrophysiological and micropuncture techniques. Canalicular cells, which secrete the primary urine, function as a Cl(-)-secreting epithelium. An apical Cl- conductance contributes to the lumen-negative potential which drives transcellular K+ transport and paracellular Na+ transport. On the basolateral side, a ouabain-sensitive Na+/K(+)-ATPase contributes substantially to the cellular and transcellular potential and provides the Na+ gradient necessary for a bumetanide-sensitive Na+/K+/2Cl- cotransport. Final urine is formed by subsequent reabsorption of ions along the central canal, where KCl and NaCl are reabsorbed in different portions. The postprandial diuresis is not a consequence of the changes in blood osmolality or ion concentrations. Similar changes in the ionic environment do not promote diuresis in isolated nephridia. Apparently, the composition and volume of the primary urine cannot be separately controlled. Any increase in fluid secretion by leech canalicular cells involves upregulation of the paracellular pathway and stimulation of Cl- entry, which thereby changes the normally K(+)-enriched primary urine to the Na(+)-enriched primary urine characteristic of leeches in diuresis.

Animals↗

PubMed1995

An endogenous peptide modulates the activity of a sensory neurone in the leech Hirudo medicinalis.

Sensory and neurosecretory innervation of each leech excretory complex, a nephridium and its bladder, is accomplished by a single neurone, the nephridial nerve cell (NNC). The NNC monitors the extracellular Cl- concentration, which ranges between 20 and 100 mmol l-1 depending on the physiological state. The NNC contains FMRFamide in its soma and sensory terminals in the nephridium. Bath or focal application of FMRFamide leads to hyperpolarization and decreases the rate of firing of the NNC, suggesting autoregulation of peptide release. Experiments under single-electrode current-clamp and voltage-clamp show that FMRFamide turns off the receptor-specific Cl- current of the NNC, indicating that FMRFamide also modulates the receptor gain.

Animals↗

PubMed1993

Sensory and neurosecretory innervation of leech nephridia is accomplished by a single neurone containing FMRFamide.

The neural control of the excretory system of the medicinal leech Hirudo medicinalis has been characterized morphologically and chemically using light and electron microscopy, immunocytochemistry and biochemistry. Immunoreactivity against RFamide-like peptides revealed elaborate neuronal aborizations of a neurone in the nephridium, around the urinary bladder sphincter and in the central nervous system. The processes arose from the nephridial nerve cell (NNC), a previously identified receptor neurone. Using a combination of reverse-phase high pressure liquid chromatography, radioimmunoassay and subsequent Edman degradation and mass spectrometry, authentic FMRFamide has been identified as the major peptide of the NNC. Sensory and neurosecretory innervation of the nephridia is thus accomplished by a single neurone, which is thought to modulate nephridial performance.

Amino Acid Sequence↗

PubMed1991

Mechanism of Cl- sensitivity in internal ion receptors of the leech: an inward current gated off by Cl- in the nephridial nerve cells.

The nephridial nerve cells of the leech, Hirudo medicinalis, 34 sensory cells, each associated with one nephridium, are sensitive to changes in extracellular Cl- concentration, an important factor in ion homeostasis. Using single-electrode current- and voltage clamp and ion substitution techniques, the specificity and mechanism of Cl- sensitivity of the nephridial nerve cell was studied in isolated preparations. Increase of the normally low external Cl- concentration leads to immediate and sustained hyperpolarization, decrease of the frequency of bursts and decrease of membrane conductance. The response is halogen specific: Cl- can be replaced by Br-, but not by organic mono- or divalent anions or inorganic divalent anions. At physiological Cl- concentrations (36 mM extracellular Cl-), the nephridial nerve cell has a high resting conductance for Cl- and the membrane potential is governed by Cl-. In high extracellular Cl- concentrations (110-130 mM), membrane conductance is low, most likely due to the gating off of Cl- channels. Under these conditions, membrane potential is dominated by the K+ distribution and the nephridial nerve cell hyperpolarizes towards EK.

Animals↗

PubMed1989

Prevention of radiocontrast-media-induced nephrotoxicity by the calcium channel blocker nitrendipine: a prospective randomised clinical trial.

Despite the development of new non-ionic low-osmolality contrast media, nephrotoxicity of intravascular radio-opaque contrast media remains a severe clinical problem, particularly in patients with risk factors. Widely accepted mechanisms of contrast-media-induced nephrotoxicity are disturbances of renal microcirculation due to prolonged intrarenal vasoconstriction, and direct damaging effects on glomerular and tubular cells. Calcium channel blocking agents have been shown experimentally and clinically to ameliorate ischaemic and toxic renal injury. In the present prospectively randomised, double-blind clinical trial, we investigated a total of 35 patients after intravascular administration of contrast media to determine the effects on renal function of a 3-day treatment with the calcium channel blocker nitrendipine (20 mg/day orally, starting 1 day before X-ray examination, n = 16), compared to findings in a placebo-treated control group (n = 19). Despite the fact that baseline renal function was significantly more compromised in the investigational group, the prophylactic application of nitrendipine preserved the glomerular filtration rate, whereas control patients showed a significant (27%) reduction in GFR on day 2 after contrast-media injection (P less than or equal to 0.01). Moreover, the increase in enzymuria of three different renal enzymes (gamma-GT, AAP, and beta-NAG), as well as urinary protein excretion, was significantly ameliorated by nitrendipine. These data confirm previous findings of our group in patients after kidney transplantation, indicating that prophylactic and/or therapeutic application of calcium channel blockers is of substantial value in preventing ischaemic or toxic renal injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast Media↗

PubMed1988

The variance-covariance method: microdosimetry in time-varying low dose-rate radiation fields.

The variance-covariance method is employed at low doses and in radiation fields of low dose rates from an 241Am (4 nGy/s) and a 90Sr (300 nGy/s) source. The preliminary applications and results illustrate some of the potential of the method, and show that the dose average of lineal energy or energy imparted can be determined over a wide range of doses and dose rates. The dose averages obtained with the variance-covariance method in time-varying fields, for which the conventional variance method is not suitable, agree well with results obtained under the condition of constant dose rate. The results are compared to data obtained in terms of the conventional single-event measurements. The method has evident advantages, such as facility and speed of measurement.

Americium↗