Biomedical subjects

A Edman

Publications and source records attributed to A Edman.

At least 19 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↗

PubMed2002

Relationship between depressive symptomatology and the subcortical brain syndrome in dementia.

OBJECTIVES: the aim of the present study was to elucidate a possible relationship between depressive symptomatology and regional brain symptomatology in demented patients. METHODS: 170 consecutive inpatients were studied. They suffered from Alzheimer's disease (103 patients), vascular dementia (48 patients), or frontotemporal dementia (19 patients). The patients underwent a neuropsychiatric investigation, which included assessments of (1) depression, and (2) regional brain symptomatology. Depressive symptomatology was assessed as presence of (a) depressed mood, and (b) anxiety. In the further statistical analysis, the presence of depressed mood and/or anxiety was also evaluated. The principle of the regional symptom analysis was the successive aggregation of observable symptom variables, leading to the final determination of four possible regional brain syndromes (frontal, subcortical, parietal and global), by way of the Stepwise comparative status analysis (STEP). The possible correlations between regional brain symptomatology and depressive symptomatology were analysed by means of (a) chi(2) statistics, and (b) a logistic regression analysis in which confounding factors were included (age, degree of dementia, duration). RESULTS: the subcortical syndrome correlated with depressed mood (chi(2), p = 0.002; logistic regression, p = 0.002). A negative correlation was noted between the parietal syndrome and depressed mood (p = 0.010 and p = 0.013, respectively). No other significant correlations between presence of regional brain syndrome and presence of depressive symptomatology could be seen. CONCLUSIONS: demented patients with a clinically established subcortical dysfunction appear to be more susceptible to depressive symptomatology. The results of this study also suggest that posterior brain dysfunction in dementia is not correlated with depressive symptomatology.

Brain↗

PubMed2001

Neurofilament protein in cerebrospinal fluid: a marker of white matter changes.

The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta-amyloid42 (Abeta42) in individuals with moderate or severe white matter changes (WMC) and in those with mild or no WMC. Twenty-two patients with Alzheimer's disease (AD), nine patients with subcortical vascular dementia (SVD), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty-seven subjects had no or only punctate WMC; 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inheritance, contributed to the variance in the CSF levels of tau, NFL, and Abeta42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not CSF tau or CSF Abeta42, was increased also after correction for age, gender, and degree of cognitive impairment. A comparison between patients and controls with any signs of WMC and those without such signs yielded a similar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC. As in numerous previous studies, we found that CSF tau was increased in AD (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diagnostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WMC and increased CSF NFL was found. Because NFL is located mainly in large myelinated axons, increased CSF NFL in individuals with WMC probably reflects axonal degeneration.

Aged↗

PubMed2001

Tacrine and rate of progression in Alzheimer's disease--relation to ApoE allele genotype.

Today, cognitive impairment can be successfully treated with acetylcholine esterase inhibitors (AChE-I) in many, but not all, patients with Alzheimer's disease (AD). To investigate the relation between tacrine treatment, inheritance of ApoE epsilon4 alleles, and rate of progression, the differences in MMSE and CIBIC scores (efficacy parameters) after 6 and 12 months of tacrine (an AChE-I) treatment were investigated in 145 AD patients. Of these, 84 were ApoE epsilon4-positive (ApoE4) and 61 were ApoE epsilon4-negative (ApoE2-3). No differences were found after 6 months of treatment, but after 12 months the CIBIC scores revealed that the ApoE4 patients had declined more than the ApoE2-3 patients (p < 0.05). No differences were found for the last 6 months of treatment. The results primarily suggest a faster rate of decline in the ApoE4 AD compared to the ApoE2-3, but may also reflect that ApoE epsilon4 genotype inheritance is a negative predictor of treatment effect of tacrine in AD patients.

Aged↗

PubMed2001

EEG abnormalities in dementia reflect the parietal lobe syndrome.

The aim of this study was to investigate to what extent the examination of regional syndromes can improve EEG diagnostics in dementia. The study was based on 77 patients, aged between 47 and 83 years, with a dementia disease in accordance with the DSM-III-R criteria. The clinical examination was refined using a so-called stepwise clinical status analysis to estimate the occurrence and intensity of the parietal lobe syndrome, the frontal lobe syndrome, the subcortical syndrome and the less-regionalised global syndrome. In the same time period, the patients were examined electroencephalographically and the recordings were assessed both visually and by means of spectrum analysis. It was found that the intensity of the parietal lobe syndrome was correlated more strongly to the EEG slow activity as compared to the other regional syndromes. Thus, it can be expected that the EEG will be most valuable in the early-onset type of Alzheimer's disease, in which the parietal syndrome is dominant, giving information regarding the degree of dementia and suggesting a possible interference with depression. The results of the study can probably explain some discrepancies between the EEG findings and the results of clinical examination in other forms of dementia.

Aged↗

PubMed2001

Hyperactivity in the hypothalamic-pituitary-adrenal axis in demented patients with delirium.

Occurrence of delirium is known to be related to, among other things, organic brain disorder, somatic disease and old age. It has been hypothesized that delirium is also associated with stress. Disturbances of the hypothalamic-pituitary-adrenal (HPA) system have been found in delirious patients in various studies. The aim of the present study was to determine the activity in the HPA axis in demented patients to ascertain whether the stress regulating system was more disturbed in patients with delirium than in those without delirium. Demented inpatients with no acute medical illness were included in the study. Basal cortisol levels in serum were measured and dexamethasone suppression test (DST) was performed. The most important finding of the study was a strong relationship between delirium and DST pathology irrespective of age and severity of dementia. It is suggested that certain demented individuals have an impaired HPA system and a low delirium threshold and respond to stress with delirium.

Aged↗

PubMed2001

Inter-rater reliability of the STEP protocol.

An inter-rater reliability test of the Stepwise Comparative Status Analysis (STEP) is presented. The STEP is a protocol for the clinical examination of patients with dementia, within the scope of a neuropsychiatric investigation. It combines psychiatric and neurologic bedside examination methods. The analysis is made in three steps where primary, observable symptom variables are successively aggregated via compound variables to the final determination of one of seven possible dominant regional brain syndromes (global, frontal, subcortical, parietal, frontosubcortical, frontoparietal, other), here also called complex variables. In the present study, two senior physicians assessed 50 patients independently and simultaneously. None of the patients was known to both physicians. In 42 patients (84%), the same dominant brain syndrome was determined by the two clinicians. The probability (P value) of this (or better) agreement was calculated at 2.0 x 10(-12). Kappa coefficients were calculated as a measure of assessment agreement regarding the 50 STEP variables. For 20 variables, the coefficient was 0.75 or above, indicating excellent agreement; for 22 variables, the coefficient was below 0.75 and above 0.40, indicating moderate agreement; and for 4 variables, the value was 0.40 or below, indicating poor agreement. Kappa calculations regarding the assessments of four variables were either not possible or were considered inappropriate.

Aged↗

PubMed2000

Symptoms, vascular risk factors and blood-brain barrier function in relation to CT white-matter changes in dementia.

The aim was to study the frequently found white-matter changes on computerized tomography (CT) in patients with dementia and to relate these changes to clinical regional brain symptomatology, vascular factors, albumin ratio [indicator of blood-brain barrier (BBB) function] and other CT changes. The study included 85 patients, average age 71 +/- 8, with Alzheimer's disease (n = 56) and vascular dementia (n = 29), who underwent CT (Siemens Somatome DR 1) of the brain. They were inpatients in a psychiatric department specialized in dementia investigations. The degree of CT white-matter changes (absence, mild-moderate, severe) was the basis for the division of the patients into three groups. As the patients without white-matter changes were significantly younger than those with such changes, all statistical analyses were controlled for age. Subcortical symptomatology was significantly more frequent in the group with severe white-matter changes, whereas the reverse was true for parietal symptomatology. Diabetes mellitus, hypertension, ischemic cardiac disease and lacunas were significantly more common in patients with white-matter changes, whereas the frequency of transient ischemic attack/stroke episodes did not differ significantly between the groups. The albumin ratio was significantly higher in the groups with white-matter changes and highest in the group with severe white-matter changes. The findings indicate that white-matter changes in demented patients are at least partially an age- and stroke-independent disease manifestation of the vascular system and is associated with a specific symptom pattern. BBB dysfunction may be the link between the vasculature and the tissue damage.

Aged↗

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↗

PubMed1997

Symptomatological characteristics distinguish between frontotemporal dementia and vascular dementia with a dominant frontal lobe syndrome.

OBJECTIVE: Our hypothesis was that patients with vascular dementia and a dominating frontal lobe syndrome have a symptomatology that reflects a more widespread lesion compared with patients with frontotemporal dementia. DESIGN: Patients with vascular dementia and a dominating frontal lobe syndrome (VAD-F; N = 11) were compared with regard to clinical symptoms and imaging features on CT scans of the brain with patients with frontotemporal dementia (FTD; N = 21). SETTING: A neuropsychiatric diagnostic ward. PATIENTS: Thirty-two inpatients, aged 48-78 years, with frontotemporal dementia or vascular dementia. MEASURES: Relatives were questioned about the initial symptoms. At the clinical investigation, mental and neurological symptoms and signs were recorded using the STEP method (stepwise comparative status analysis). CT scan features of the brain were evaluated by a trained neuroradiologist. The GBS-i (Gottfries-Bråne-Steen, intellectual variables) scale was used to measure the degree of dementia. RESULTS: At the onset of dementia, loss of memory (p < 0.001), sudden onset (p < 0.001), confusion (p < 0.05) and unspecified neurological signs (p < 0.05) had been significantly more frequent in the VAD-F group. At the time of the clinical investigation, lack of social awareness and presence of primitive reflexes were more frequent in the FTD group (p < 0.01 and p < 0.05, respectively) and visuospatial deficits more frequent in the VAD-F group (p < 0.05). CT of the brain showed that, apart from brain infarcts (present only in the VAD-F group), paraventricular leukoaraiosis was significantly more pronounced in the VAD-F group (p < 0.05). The groups did not differ with respect to age, age at onset or level of dementia. CONCLUSION: The findings support our hypothesis.

Age of Onset↗

PubMed1996

Decreased lumbar cerebrospinal fluid levels of monoamine metabolites in vascular dementia.

The levels of the monoamine metabolites 5-hydroxy-indoleacetic acid (5-HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxy-phenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 56 patients with vascular dementia (VAD) and 57 healthy controls. Despite CSF sampling under standardized conditions, the variability in values was wide among both patients and controls. This suggests that yet unknown factors affect the lumbar CSF concentrations of monoamine metabolites. The VAD group showed significantly lower mean concentrations of 5-HIAA (p < .001) and HVA (p < .001) than the control group. These low concentrations appear to be no disease-specific phenomenon, but may be attributable to subcortical white-matter changes or a decreased production of monoamines, which are dependent on oxygen for their synthesis.

Aged↗

PubMed1996

Stepwise comparative status analysis (STEP): a tool for identification of regional brain syndromes in dementia.

A method for clinical examination of patients with dementia, stepwise comparative status analysis (STEP), is presented. It combines psychiatric and neurologic status examination methods to identify certain common dementia symptoms by which the patient's regional brain symptom profile can be determined. Fifty status variables (items) are estimated with respect to occurrence and severity. The analysis is performed in three steps. The scores on the 'primary' variables reflect observations of single dementia symptoms. These scores form the basis for the assessment of the 'compound' variables, which in turn form the basis for evaluation of the 'complex' variables, one of which describes the patient's regional (predominant) brain syndrome (subcortical, frontosubcortical, frontal, frontoparietal, parietal, or global). In 96 mildly and moderately demented inpatients, the global (42%) and frontosubcortical (31%) were the most common. Ninety-one percent of the patients with vascular dementia had a predominant frontal and/or subcortical symptomatology.

Aged↗

PubMed1992

Functional effects of a hyperpolarization-activated membrane current in the lobster stretch receptor neurone.

The functional effects of a hyperpolarization-activated membrane current (IQ) in the slowly adapting lobster stretch receptor neurone were investigated. From comparisons between changes in membrane excitability due to blockage of IQ by Cs+, in normally impaled and native unimpaled (Edman et al. 1987 b) cells, it could be concluded that the resting voltage of native cells is distinctly more negative than -65 mV (average membrane voltage of impaled cells) and, therefore, under the control of an activated IQ. Starting from this conclusion, impaled cells were polarized to holding (resting) voltages around -75 mV and their polarization and excitability properties studied after tetanic impulse activity and variation of various external influences (K+, pH, temperature), both in control conditions and after blockage of IQ by 2 mM Cs+. It was found that an unblocked IQ (a) greatly accelerates the initial (90%) decay of post-tetanic hyperpolarization, and (b) depresses distinctly any polarization and excitability alterations due to increases in extracellular K+ concentration (from 2.5 to 10 mM), variations in extracellular pH (between 6.4 and 8.6), and changes in temperature (between 14 and 24 degrees C). It was inferred that in well polarized cells, IQ plays a role as a stabilizer of membrane polarization and excitability in conditions of varying external influences. From a model study of IQ it could be concluded that, with its slow dynamic responses, the current is well adapted to its functional purposes and to the rather slow homeostatic effects of the cell's Na-K pump.

Animals↗

PubMed1991

Ion (H+, Ca2+, Co2+) and temperature effects on a hyperpolarization-activated membrane current in the lobster stretch receptor neurone.

The effects of some ions (H+, Ca2+, Co2+) and temperature on the Q-channel (a channel which conducts a hyperpolarization-activated membrane current, IQ) was investigated in the slowly adapting lobster stretch receptor neurone. It was found: (1) that increases in pH cause an increase in the maximum channel conductance; (2) that Co2+ (1 mM) and increases in extracellular Ca2+ produce a positive shift of the relationship between the membrane voltage and the steady-state channel activation along the voltage scale; (3) that Co2+ and decreases in extracellular pH cause a decrease in rate of the voltage-dependent step of the channel's gating reaction; (4) that none of the ions has an effect on the rate of the voltage-independent step of the gating reaction; and (5) that Co2+ and K+ do not interfere with each other's actions on the channel's gating reaction and maximum ion conductivity. Increases in temperature from 13 to 23 degrees C were found: (1) to cause an increase in the maximum Q-channel conductance by a factor of 1.7; (2) to have no effect on the voltage dependence of the channel's gating reaction; but (3) to lead to an increase in rate of the gating reaction by a factor of about five for the voltage-dependent, and by a factor of about three for the voltage-independent gating step. The temperature sensitivity of the IQ mechanism proved to be mathematically reproducible by a previously developed, and slightly modified Q-channel model (Edman et al. 1987, Edman & Grampp 1989), and to be of no significance in the control of membrane excitability in a thermally unstable environment.

Animals↗

PubMed1989

Ion permeation through hyperpolarization-activated membrane channels (Q-channels) in the lobster stretch receptor neurone.

In the lobster stretch receptor neurone it is possible to demonstrate a hyperpolarization-activated membrane current, IQ, which appears to be carried by Na+ and K+ in combination. The ion permeability of the membrane channel conducting this current (Q-channel) was investigated using conventional electrophysiological techniques including intracellular ion concentration measurements. It was found that none of the ions choline, protonated Tris, Rb+, NH4+, Li+, and protonated hydroxylamine was able to pass through the Q-channel which, thus, appears to be permeable to Na+ and K+ only. With increasing extracellular Na+ concentrations, IQ was increased up to a saturation level. This behaviour could be described by a one-site-two-barriers version of the Eyring rate theory, assuming that the permeant ions are turned over at specific saturable channel sites which 'sense' 70% of the transmembrane potential difference. With increasing extracellular K+ concentrations, IQ was increased in accordance with a simple first-order dose-response relationship. This finding can be accounted for by assuming that K+ increases all rates of turn-over of the permeant ions at their specific sites by similar relative amounts. Changes in extracellular Na+ and K+ concentrations were found to have no effect on the gating properties of the Q-channel.

Animals↗

PubMed1987

Analysis of gated membrane currents and mechanisms of firing control in the rapidly adapting lobster stretch receptor neurone.

1. The gated membrane currents (a tetrodotoxin-sensitive Na+ current and a tetraethylammonium- and 4-aminopyridine-sensitive K+ current) of the rapidly adapting stretch receptor neurone of lobster were investigated with respect to their kinetic properties using electrophysiological, pharmacological, and mathematical techniques. 2. The currents were found to be controlled by slow inactivations as well as by fast Hodgkin-Huxley (1952) gating processes. They could be described by kinetic expressions which differed from those inferred for the slowly adapting receptor (Gestrelius & Grampp, 1983a; Gestrelius, Grampp & Sjölin, 1983) only with respect to some of the parameter values. 3. With these expressions, and additional equations for the cell's pump and leak current components (Edman, Gestrelius & Grampp, 1986), a mathematical receptor model was formulated which accurately predicts the impulse activity of the living preparation in different functional circumstances and which, therefore, was adopted as an appropriate theory of firing regulation. 4. From a model analysis it appeared (a) that the 'rapid' adaptation of the receptor's impulse activity is mainly an effect of slow Na+ current inactivation starting a regenerative process of accommodation which, basically, is due to a small ratio of subthreshold Na+ to K+ currents; (b) that, because of the transmembrane Na+ influx being limited by accommodation, impulse firing is only little affected by a Na+-dependent pump current activation; and (c) that the phenomenon of increased firing frequency initially during prolonged stimulation ('negative adaptation') is an effect of the slow K+ current inactivation being faster than the slow Na+ current inactivation at comparable degrees of membrane polarization. 5. From further model studies it also appeared that, during depolarizations between successive action potentials evoked by constant stimulation, the membrane behaves like a high-resistance constant-current generator feeding into a short-circuiting capacitor. In consequence, the cell's stimulus sensitivity (change in firing frequency with stimulation strength) is, at functionally relevant stimulation intensities, mainly determined by the membrane capacitance and by the amplitude of the interspike membrane depolarization while, at higher stimulation intensities and firing frequencies, it becomes more and more a function of the spike duration itself.

Action Potentials↗

PubMed1987

Current activation by membrane hyperpolarization in the slowly adapting lobster stretch receptor neurone.

1. A polarization-induced membrane current, IQ, was investigated in the slowly adapting lobster stretch receptor neurone using conventional electrophysiological techniques including intracellular ion measurements. 2. The current was readily blocked by Cs+ in a voltage-dependent manner, but proved to be unaffected by tetrodotoxin, tetraethylammonium and 4-aminopyridine. 3. From an analysis of the ionic basis of IQ, it appeared that the current is carried by both Na+ and K+ through a membrane channel whose permeability for K+ is about six times larger than that for Na+ in a normal ionic environment. In the presence of reduced external Na+ concentration the Q-channel increases its permeability for both Na+ and K+, but more so for Na+ than for K+. 4. Kinetically, IQ was found to be characterized by a steep sigmoidal relationship between membrane voltage and steady-state current activation, and by a bell-shaped relationship between membrane voltage and the time constant of the exponential phase of current activation or deactivation. A significant feature of the latter relationship is a tendency to level off at finite time-constant values in both strongly hyperpolarizing and strongly depolarizing voltage regions. 5. From the experiments a mathematical IQ model was inferred. This model was based on constant-field and channel-gating kinetics involving a voltage-dependent reaction step in series with a voltage-independent reaction step. The model was found to successfully reproduce IQ behaviour in the living preparation. 6. Functionally, the activation of IQ was found to play a role in setting the cell's resting polarization and membrane excitability. This function was inferred from experiments on unimpaled cells in which it was possible to demonstrate some overlap between the voltage ranges of IQ activation and impulse initiation. In addition, in impaled cells the activation of IQ was found to cause some shortening of post-tetanic membrane hyperpolarization and to accelerate, thereby, the post-tetanic restoration of membrane excitability to control levels.

Action Potentials↗

PubMed1986

Transmembrane ion balance in slowly and rapidly adapting lobster stretch receptor neurones.

The transmembrane exchange of Na+, K+, and Cl- in slowly and rapidly adapting lobster stretch receptor neurones was studied using ion-sensitive microelectrodes in combination with conventional electrophysiological techniques. The investigation was founded on the assumption that the transmembrane ion exchange is accomplished by active and passive transports which add up to zero in steady state for each ion involved. The active transports are assumed to include Na+ and K+ transports driven by an electrogenic Na-K pump. To these transports are also added equimolar fluxes of K+ and Cl- leaking from the impaling micro-electrode. The passive transports are assumed to pass through membrane channels in accordance with constant field kinetics. For a quantitative evaluation of the transmembrane ion exchange in resting conditions measurements were made of the resting concentrations of Na+, K+ and Cl-; the voltage dependence of the ungated leak current; and ouabain-induced changes in resting membrane current and intracellular ion concentrations. From the results it follows that both the resting pump current and the leak permeabilities for the ions investigated have values which do not seem to differ between slowly and rapidly adapting receptor neurones. For a quantitative evaluation of the relation between internal Na+ and pump current production, measurements were made of the outward membrane current as a function of internal Na+ and K+ following a shift of these ions by means of prolonged repetitive impulse activation. It was found that the investigated relation is compatible with Garay-Garrahan kinetics (Garay & Garrahan, 1973) in both receptor neurones, but the results imply a larger maximum Na+-extrusion capacity in slowly than in rapidly adapting cells. From recordings of the time course of post-tetanic normalization of both the membrane current and intracellular Na+ concentration, cell volume values could be deduced which were closely similar in slowly and rapidly adapting receptors. A corresponding similarity was also found for the cell area which was derived from membrane capacitance measurements.

Adaptation, Physiological↗