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K Mückenhoff

Publications and source records attributed to K Mückenhoff.

16 recordsLinked to original sources
PubMed1996

Chemosensitive medullary neurones in the brainstem--spinal cord preparation of the neonatal rat.

1. Using the isolated medulla and spinal cord of the neonatal rat, the response to CO2-induced changes in superfusate pH was examined in whole cell and perforated patch recordings from ventral medullary neurones which were identified by injection of Lucifer Yellow. The respiratory response to changing the CO2 concentration (from 2 to 8%) consisted of an increase in phrenic burst frequency, which could be accompanied by an increase, decrease or no change in burst amplitude. 2. Five classes of neurone - inspiratory, post-inspiratory, expiratory, respiration-modulated and ionic - were distinguished on the basis of their membrane potential and discharge patterns. Almost all (112 of 123) responded rapidly to 8% CO2 with a sustained change in membrane potential. Depolarizing responses (3-18 mV) occurred in inspiratory, respiration-modulated and 45% of tonic neurones. Hyperpolarizing responses (2-19 mV) occurred in expiratory and post-inspiratory neurones. The remaining tonic neurones were inhibited or showed no response. 3. In representatives of each class of neurone, membrane potential responses to 8% CO2 were retained when tested in the presence of tetrodotoxin (n = 7), low (0.2 mM) Ca(2+)-high (5 mM) Mg2+ (n = 23) or Cd2+ (0.2 mM) (n = 3)-containing superfusate, implying that they are mediated by intrinsic membrane or cellular mechanisms. 4. Neurones were distributed between 1200 microns rostral and 400 microns caudal to obex, and their cell bodies were located between 50 and 700 microns below the ventral surface (n = 104). Almost all responsive neurones (n = 78) showed dendritic projections to within 50 microns of the surface. 6. These experiments indicate that significant numbers of ventral medullary neurones, including respiratory neurones, are intrinsically chemosensitive. The consistency with which these neurones show surface dendritic projections suggests that this sensitivity may arise in part at this level.

Animals↗
PubMed1995

Theophylline and hypoxic ventilatory response in the rat isolated brainstem-spinal cord.

We have used the isolated brainstem-spinal cord preparation of the neonatal rat to study the effects of theophylline on the ventilatory response to hypoxia. The brainstem-spinal cord was isolated from neonatal rats (0-4 days) and superfused with mock cerebrospinal fluid (CSF), equilibrated with a gas mixture (FO2, 0.90; FCO2, 0.02; FN2, 0.08; control CSF) at 27 degrees C. We recorded phrenic nerve discharge from C4 roots, using suction electrodes, and measured respiratory frequency (fR) and the amplitude of the integrated phrenic neurogram (integral of phr). We examined how theophylline and the specific adenosine antagonist, 8-p-sulfophenyltheophylline (SPT), modify the ventilatory response to hypoxia. The response during superfusion with hypoxic CSF (FO2, 0.06) consisted of a marked decrease in fR (to 60% of control) and a slight decline in integral of phr (to 85% of control). By contrast, in the presence of theophylline (30 mg/L = 165 microM) and SPT (5 mg/L = 15 microM) in the superfusate hypoxia reduced fR only moderately (to 87% of control) and exerted virtually no effect on integral of phr (105% of control). Theophylline and SPT attenuated the rate of decrease in fR and completely blocked the decrease in integral of phr. There was no difference between the effects of theophylline and those of SPT. The results suggest that theophylline attenuates hypoxic respiratory depression, and that this effect is mediated by the blockade of adenosine.

Animals↗
PubMed1994

Activity-related pH changes in respiratory neurones and glial cells of cats.

Intracellular pH (pHi) and membrane potential (Em) were measured in vivo in expiratory neurones and glial cells in the medulla of anaesthetized cats using double-barrelled H(+)-sensitive microelectrodes. In glial cells, stimulation of spinal pathways evoked a depolarization of up to 12 mV amplitude and an increase of pHi (7.25 +/- 0.15) by maximally 0.1 pH unit. IN expiratory neurones, pHi (7.15 +/- 0.18) fell by up to 0.2 pH unit during inspiratory inhibition. In axons of expiratory neurones, pHi remained unaffected during rhythmic action potential discharges. We suggest that the glial alkalinization is due to activation of Na+/HCO3- cotransport, whereas the neuronal acidification is caused by efflux of HCO3- via receptor-coupled anion channels.

Animals↗
PubMed1994

Pump for accurate mixing of three gas components with predetermined fractions.

A mixing pump that creates an accurate mixture of three gases at predetermined fractional ratios that can be set in steps of 10 ppm is described. A nearly continuous flow of each of the three component gases is produced by pistons driven by stepping motors; the gas mixture is forwarded by a fourth piston. The flow of each component gas is adjusted by the stepping frequency of the motor and a microcomputer system is used to adjust the three frequencies according to the desired fractional concentrations. The total flow of the gas mixture is adjustable between 0.1-500 ml/min and is nearly independent of the after-load. The accuracy of the pump was tested by mixing the respiratory gases, O2 and CO2, with various carrier gases (N, He or Ar) at various fractional ratios and total flow rates. The fractions of O2 and CO2 in the mixture were analysed with the Scholander technique. In the physiological range, the mixing error in the gas fractions was less than 4%. The pump is, thus, suited for producing calibration mixtures.

Carbon Dioxide↗
PubMed1994

Ion-sensitive microelectrode system with short response time.

The measurement of changes in ion activity (e.g., pH) in neurons requires fine tip-sized double-barreled microelectrodes: one channel being equipped with an ion-selective liquid membrane, the other used for measurement of the membrane potential. The limited bandwidth and the differing transfer functions for electrical and ionic signals necessitate frequency response linearization networks to ensure that the output signal of the electrode is a faithful image of the input signal. We have developed a linearization network to ensure a rapid response time for ion-sensitive microelectrodes. To test the response characteristic we have developed a test system that allows the pH at the electrode tip to be changed within 1 ms. Application of these techniques to electrodes of 1 micron tip diameter results in a 90% response time to a pH step of approximately 60 ms and of approximately 2 ms with electrodes with 20 micron tip.

Electrophysiology↗
PubMed1993

Depth profiles of pH and PO2 in the isolated brain stem-spinal cord of the neonatal rat.

We have measured depth profiles of extracellular pH (pHECR) and PO2 (PtO2) as well as the kinetics of changes of pHECR in the isolated brain stem-spinal cord preparation of the neonatal rat using pH and PO2 microelectrodes that entered from the ventral surface. When the preparation was superfused with control mock cerebrospinal fluid (Control mock CSF; pH = 7.5, PO2 = 630 Torr, PCO2 = 28 Torr, at 27 degrees C), the pH in the medulla diminished with a nearly constant gradient from the surface to a depth of about 1000 microns, the slope being about 0.1 pH unit per 100 microns. A similar gradient in the 200 to 300 microns of the CSF above the surface suggested existence of unstirred layers despite continuously flowing superfusate. The pH gradient in the spinal cord was somewhat smaller than that in the medulla. The PO2 gradients in both medulla and spinal cord were about 100 Torr per 100 microns from 200 microns above to 100 to 200 microns below the surface; PO2 reached zero at about 450 (medulla) to 600 microns (spinal cord). Although the preparation was anoxic and acidic except for a small layer below the surface, respiratory activity was recorded for several hours in C4 phrenic roots. The kinetics of changes in pHECF were recorded at 100 and 200 microns depth while rapidly replacing the control mock CSF by more acidic CSF, either with increased PCO2 ("Respiratory acidosis") or by adding fixed acid ("Metabolic acidosis"). The changes in pHECF were smaller than those in pHCSF, particularly during respiratory acidosis, as a result of the buffering of the brain tissue. Our results show the importance of superficial layers of the ventral medulla in producing respiratory rhythmicity; they further suggest that somewhat alkaline CSF (pH about 7.8) should be used in this preparation to ensure physiologic surface pH values despite unstirred surface layers.

Animals↗
PubMed1993

Hypercapnia and medullary neurons in the isolated brain stem-spinal cord of the rat.

We have extracellularly recorded single neuron activity in the ventral medulla of the isolated brain stem-spinal cord preparation of the neonatal rat (37 preparations) in order to test their sensitivity to changes in CO2/H+. Search for neuronal activity was performed when the preparation was superfused with control mock CSF (equilibrated with 2% CO2, 90% O2 in N2; pH = 7.8 at 27 degrees C). Neurons, found down to about 500 microns from the surface, could be classified as R neurons when they showed rhythmic discharge in phase with phrenic activity, recorded from C4 ventral roots; or as Non-R neurons when they did not exhibit such phasic discharge. Among the 89 Non-R neurons, 20 responded to rapidly replacing the control CSF by hypercapnic CSF (8% CO2, 90% O2 in N2; pH = 7.2) with increased, 44 with reduced activity, while 25 did not respond to hypercapnia. Five Non-R neurons became phasic with respiration during hypercapnia. Of the 14 R neurons, 10 fired predominantly in expiration (R-E), 4 in inspiration (R-I). Only one R-E and two R-I neurons were excited by hypercapnia, the remaining were either inhibited or did not respond. Excited Non-R and R neurons were mainly encountered in rostral parts of those areas in the ventral medulla that have been reported as chemosensitive.

Animals↗
PubMed1989

Afferent vagal activity during hyperthermic polypnea in the pigeon.

Respiration-modulated activity in afferent vagal fibers was recorded in 10 pigeons during euthermic breathing and thermal panting. Of these fibers, 13 were identified as intra-pulmonary chemoreceptors (IPCs), that increased discharge with diminishing lung gas PCO2, and 13 as mechanoreceptors, that increased firing with lung inflation. Two types of IPC were observed that were distinct by their firing pattern during panting. Phasic IPCs displayed phasic discharge within the respiratory cycle, even at respiratory frequencies (fresp) as high as 400 min-1. Tonic IPC fired tonically and increased their discharge as fresp increased. Several IPCs were silent during euthermic breathing, but discharged tonically as fresp increased with thermal polypnea. Discharge of neither type of IPC was consistently related to PaCO2. Discharge from mechanoreceptors was phasic with respiration, up to values of fresp as high as 350 min-1. However, the average number of impulses per breath decreased as fresp increased. We conclude that discharge from phasic intrapulmonary chemoreceptors and mechanoreceptors may contribute to setting the respiratory pattern during hyperthermic polypnea.

Animals↗
PubMed1984

Evidence for a role of NA+/H+ exchange in platelets activated with calcium-ionophore A 23187.

We have investigated the release of protons from human platelets and platelet aggregation induced by the calcium ionophore, A 23187. Addition of the ionophore to suspensions of washed platelets resulted in fast liberation of H+. In the presence of 0.2 mM amiloride, a potent inhibitor of Na+/H+ countertransport, the amount of protons liberated was decreased by 50% and was further reduced to about 10% by 1 mM amiloride. Similar inhibition of H+-release was observed after decreasing Na+ in the incubation medium. Both results suggest that increasing internal Ca2+ by the ionophore induces Na+/H+ exchange in human platelets. Platelet aggregation could be induced by adding the ionophore to the platelet suspension. This aggregation was inhibited by amiloride, at least when induced by low ionophore concentrations. The results suggest that stimulation of Na+/H+ exchange, and the concomitant increase in intraplatelet pH, are important mechanisms in platelet activation.

Amiloride↗
PubMed1984

Thrombin stimulates Na+-H+ exchange across the human platelet plasma membrane.

We have investigated the release of protons from thrombin-stimulated platelets. Addition of thrombin to suspensions of washed platelets resulted in fast liberation of H+. In the presence of 0.1 mM amiloride, a potent inhibitor of the Na+/H+ transport system, the amount of protons liberated was decreased by about 50%, and was further reduced to about 15% by 1 mM amiloride. Similar inhibition of H+ release was observed after Na+ in the incubating medium had been replaced by choline. We conclude that one of the earliest events in thrombin-stimulated platelets consists of the activation of an Na+/H+ countertransport, which leads to an increase in intracellular pH.

Amiloride↗
PubMed1981

The influence of changes in pCO2 on the fractional packed cell volume of whole blood.

In order to investigate the influence of changes in pCO2 on the fractional packed cell volume (FPCV, hematocrit) of whole blood, a device for measuring the conductivity was developed. This method allows an instantaneous and continuous determination of the FPCV, because the erythrocyte membrane has insulating properties, and, consequently, the resistance of blood depends on the relative cell volume. The steady state and transient relationships between FPCV and acid-base levels were investigated by combining this method with simultaneous recordings of pCO2. The experiments showed that addition of CO2 caused an increase in the resistance of whole blood, whereas the resistance of separated plasma decreased slightly and the resistance of true plasma remained almost constant. The change in the FPCV (delta H) can be described by a linear function of pH or log pCO2 (formula: see text). The transient response of the resistance, after a stepwise increase in the CO2 content, was found to be the slowest process in attaining an acid-base equilibrium. In blood with acetazolamide, the time courses of changes in pH and pCO2 were retarded, whereas the time course of the resistance change reflecting the swelling of the erythrocytes was nearly the same (T 50 approximately equal to 4 s). This may indicate a rate-limited water shift due to a slight water permeability of the erythrocyte membrane.

Acetazolamide↗
PubMed1977

An automatically balancing isolation amplifier for the decoupling of measuring systems with high impedances.

It is theoretically shown that different conditions of coupling and grounding cause error voltages with the simultaneous use of two high-impedance measuring systems (e.g. pH electrodes). By the use of special amplifiers using optical transmission systems these error voltages are prevented. The transmission characteristics of the couplers are sensitive to changes in temperature due to the incorporation of infrared emitters in the system. An amplifying equipment with high d. c. stability was developed. The temperature drift was suppressed by the use of a special chopper stabilisation.

Electric Conductivity↗