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C Fahlke

Publications and source records attributed to C Fahlke.

At least 55 records · Page 3Linked to original sources
PubMed1992

Giga-seal formation alters properties of sodium channels of human myoballs.

The influence of giga-seal formation on the properties of the Na+ channels within the covered membrane patch was investigated with a whole-cell pipette and a patch pipette applied to the same cell. Current kinetics, current/voltage relation and channel densities were determined in three combinations: (i) voltage-clamping and current recording with the whole-cell pipette, (ii) voltage-clamping with the whole-cell pipette and current recording with the patch pipette and, (iii) voltage-clamping and current recording with the patch pipette. The Hodgkin-Huxley (1952) parameters tau m and tau h were smaller for the patch currents than for the whole cell, and the h infinity curve was shifted in the negative direction. The channel density was of the order of 10 times smaller. All effects were independent of the extracellular Ca2+ concentration. The capacitive current generated in the patch by the whole-cell Na+ current and its effect on the transmembrane voltage of the patch were evaluated. The kinetic parameters of the Na+ channels in the patch did not depend on whether the voltage was clamped with the whole-cell pipette or the patch pipette. Thus, the results are not due to spurious voltage.

Electric Conductivity↗
PubMed1992

Whole-cell recordings of chloride currents in cultured human skeletal muscle.

Chloride currents in human myoballs were investigated with the tight-seal whole-cell recording method in a wide range of membrane voltages (-125 to +145 mV). Two current components having different kinetics could be distinguished. In more than 90% of the myoballs the following results were obtained. At negative potentials, the amplitude of the Cl- current was small and independent of time. The amplitude of the current increased as the membrane potential was made more positive. At potentials positive to +75 mV, the current increased monoexponentially with time. Inactivation occurred only during very long (greater than 3 s) pulses. When such a test pulse was preceded by a conditioning pulse to +60 mV, the current at potentials more than +90 mV was markedly smaller than in the absence of a prepulse, and no activation was provoked by strongly pulses. Recovery from inactivation could only be measured at potentials negative to -40 mV. The Cl- conductance at -85 mV was 5.9 +/- 3.64 microS/cm2 (SD; n = 10). In about 5% of the myoballs a kinetically different current was visible, characterized by fast inactivation at highly positive potentials. The current amplitudes were substantially larger in such cases, the Cl- conductance at -85 mV being 12.2 +/- 9.02 microS/cm2 (n = 4).

Calcium↗
PubMed1992

Single-channel recordings of chloride currents in cultured human skeletal muscle.

The Cl- channels in human myoballs were investigated with several recording techniques. Three types of channels were found and dubbed "small", "intermediate", and "large", according to their different conductance. The intermediate Cl- channel was observed most frequently. It was active at the resting potential immediately after seal formation in cell-attached as well as in excised patches. Its Cl- selectivity was rather high (PCl/PNa = 9.46; PCl/PMeSO4 = 7.85 where P denotes permeability) and the slope conductance at the reversal potential with [Cl-]o/[Cl-]i equal to 160 mM/42 mM was 31 pS. The channel showed an open-channel substructure with two subconductance levels having equal amplitudes. It can conduct two kinetically different currents that correspond to the activating and the inactivating Cl- current components described by Zachar et al. (1992). The small Cl- channel had a conductance of 10 pS at the reversal potential, a PCl/PNa of 2.7, and a PCl/PMeSO4 of 22.6. Its open probability was biggest negative to -85 mV, resulting in an inactivating whole-cell Cl- current component. Because of the small channel density and conductance the contribution of this channel type to the whole-cell current seems to be small. Patches with only one small channel were never observed which suggests that this channel type occurs in clusters. A third type of channel with very large conductance (250 pS) was seen only four times.

Chlorides↗
PubMed1992

Chloride channels in cultured human skeletal muscle are regulated by G proteins.

The regulation of Cl- channels in human myoballs by G proteins was studied using whole-cell and inside-out patch recordings. After perfusion of the cell with 0.1 mM GTP[gamma S], the specific Cl- conductance, GCl, at standard resting potential (-85 mV) was increased from 5.9 microS/cm2 to 103 microS/cm2, and the kinetics upon stepping the potential to positive values was changed from an activating current with very slow inactivation to a fast inactivating current with no potential-dependent activation. These effects were not affected by the simultaneous blockade of several signal cascades involving G proteins. Addition of the protein kinase blockers PKI (25 microM), H8 (10 microM), or of the phospholipase-A2-blocking agent quinacrine (10 microM), had not much influence on these GTP[gamma S] effects. Buffering of the intracellular Ca2+ concentration (0.1 microM) or addition of the Ca2+/calmodulin antagonist trifluoperazine (50 microM) was also without effect. Pre-incubation of the cells with pertussis toxin or with cholera toxin did not change GCl. In excised inside-out patches voltage-clamped at -85 mV, application of GTP[gamma S] influenced the "intermediate" Cl- channel, the Cl- channel type having the highest density in these cells, by increasing the number of transitions in a half-conductance state. The probability of the channel being in one of the two conducting states rose from 0.015 to 0.67, and the kinetics of the single-channel currents was changed so that, on average, it was similar to the whole-cell current kinetics seen after application of GTP[gamma S]. It is concluded that a G protein is directly interacting with these channels.

Chlorides↗
PubMed1988

Saturation effects and rectifier properties of sodium channels in human skeletal muscle.

Sodium outward currents were measured in human myoballs with the whole-cell recording method. The electro-chemical gradient of the sodium ions across the cell membrane was modified over a wide range by variations of the clamped membrane potential and of the internal and external sodium concentration. Up to 50 mV positive to the sodium equilibrium potential, ENa, the current-voltage relation is linear. At a potential 80 mV positive to ENa the sodium outward current has a maximum and decreases with a further increase in electrochemical gradient. Investigating the instantaneous current change in experiments in which the membrane potential was changed while the channels were already open we could exclude the possibility that the gates of activation or inactivation are responsible for this effect. Therefore we postulate that the sodium channel has a valve-like mechanism producing a negative slope conductance at highly positive membrane potentials, a current saturation with self-inhibition by the intracellular sodium concentration, and a blockade of the channel on reduction of the extracellular sodium concentration.

Cell Aggregation↗
PubMed1988

Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists.

In the present series of experiments we have studied the effects of the dihydropyridine calcium channel antagonist nifedipine on ethanol-induced changes in behavior and dopamine (DA) release and metabolism. The locomotor-stimulatory effect of low doses of ethanol (2.5 g/kg) was antagonized by nifedipine, whereas ethanol-induced sedation observed after higher doses (4.5 g/kg) was potentiated. Biochemical studies indicated that ethanol enhanced the metabolism and release of DA in the striatum and the DA-rich limbic regions measured by post mortem analyses of DA-metabolites by HPLC with electrochemical detection and by in vivo voltammetry in anaesthetized rats, respectively. Pretreatment with nifedipine antagonized the stimulatory effects of ethanol on the DA-system. Nifedipine reduced the preference for ethanol, estimated by the relative intake of ethanol (6% v/v) and water in a free-choice situation, suggesting an influence of nifedipine not only on the stimulatory but also on the positive reinforcing effects of ethanol. The present results suggest that the locomotor-stimulatory and positive reinforcing effects of ethanol as well as its enhancing effect on dopaminergic activity may involve an enhancement of calcium mediated mechanisms.

Animals↗
PubMedDate not supplied

In quest for a possible association between heightened social aggression and excessive alcohol drinking in the rat.

Many clinical studies show that a sizeable proportion of male alcoholics are also inclined to act violently and aggressively. Given this association in humans, we asked whether a relationship exists between ethanol intake and aggressive behaviour in laboratory rats. In a first test of the hypothesis, we measured ethanol intake in male rats made aggressive by periodic contacts with sexually active females. Although the males became significantly more aggressive, there was no concomitant enhancement of alcohol consumption. In another experiment, observations of ethanol drinking in lactating rats exhibiting maternal aggression revealed no alteration in ethanol intake relative to nonlactating control females. However, because water intake was substantially elevated in the maternal rats, there was a net decrease in ethanol preference. The final experiment examined aggressiveness in chronically food-restricted male rats. In line with previous studies, this procedure increased ethanol drinking, but it did not enhance aggressive behaviour. It is concluded that, in our rats, there is no apparent association between the level of social aggression and the voluntary intake of ethanol in a two-bottle choice paradigm. The possibility remains, though, that alcohol drinking is better related to other forms of aggression, such as defensive or predatory aggression.

Aggression↗
PubMedDate not supplied

Audiogenic immobility reaction and open-field behavior in AA and ANA rat lines.

Individual predispositions in emotional reactivity have been suggested as factors involved in the development of alcoholism. To approach this problem, we assessed emotional reactivity in alcohol-naive animals from the alcohol-preferring (AA) and alcohol-avoiding (ANA) rat lines of Alko Ltd. AA rats are known to have higher brain levels of 5-hydroxytryptamine (5-HT) than ANA rats. Emotional reactivity was therefore assessed by an audiogenic immobility reaction (freezing), which is specifically sensitive to and shortened by depletion of 5-HT. The results showed that AA rats of both sexes displayed increased immobility reactions compared to the corresponding sex of the ANA rats. During the period of adaptation to the test cage ANA rats of both sexes showed increased locomotor activity compared to the corresponding sex of the AA rats. Levels of plasma corticosterone did not differ between the rat lines, either during resting or stressful conditions. The present results suggest that a passive, inhibited style of defensive behavior is associated with a high alcohol consumption.

Acoustic Stimulation↗
PubMedDate not supplied

Involvement of the serotonergic system in ethanol intake in the rat.

A two-bottle, free-choice paradigm was used to investigate the influence of the serotonergic (5-HT) system on ethanol intake in genetically heterogeneous Wistar rats. Systemic administration of the 5-HT1A agonist ipsapirone (1.25-5.0 mg/kg) caused a dose-dependent decrease in ethanol preference and intake, while the 5-HT2 antagonist ritanserin (1.25-5.0 mg/kg) and the 5-HT3 antagonists ondansetron (0.01-1.0 mg/kg) and granisetron (0.5-1.0 mg/kg) failed to alter ethanol consumption. The effect of ipsapirone treatment on ethanol intake was more pronounced in high-preferring animals than in low-preferring. A closer look at the microstructure of the rat's drinking behaviour by means of a microcomputer-controlled data acquisition system showed that ipsapirone treatment caused a significant decrease in the number of licks recorded at the ethanol-containing bottle and a decrease in the time spent at this bottle. Furthermore, ipsapirone treatment caused a significant increase in the number of breaks in licking behaviour recorded at this bottle. The drinking behaviour at the water-containing bottle was not affected by the ipsapirone treatment. Neither was the rat's eating behaviour altered by this treatment. These findings support the hypothesis that the 5-HT system is involved in the regulation of ethanol intake, with special emphasis on the involvement of the 5-HT1A receptor subtype, and may indicate that central reward-mediating mechanisms are influenced.

Alcohol Drinking↗
PubMedDate not supplied

Involvement of corticosterone in the modulation of ethanol consumption in the rat.

Several studies report that rats exposed to stressful conditions may increase their ethanol consumption. Stress is accompanied by a rise in the secretion of adrenocortical hormones, and the possibility that these hormones exert an influence on ethanol consumption should be considered. The present investigation addressed this issue by studying the effect of adrenalectomy (ADX) and subsequent corticosterone (CORT) or aldosterone (ALDO) treatment on ethanol intake. The results showed that ADX rats decreased their ethanol intake compared to the sham-operated controls and that treatment with CORT restored the intake of ethanol to the preoperative level. In contrast, treatment with ALDO (0.25 or 0.75 mg/kg) had no effect on ethanol intake. Biochemical analyses showed increases in monoamine turnover in the brain stem and limbic forebrain after ADX. The reduction of ethanol consumption caused by ADX may thus be specifically attributed to the loss of one of the adrenal hormones, CORT. The results indicate that CORT may be a factor of importance in the modulation of alcohol consumption.

Adrenalectomy↗
PubMedDate not supplied

Taste reactivity to ethanol in rats: influence of adrenalectomy or ipsapirone.

The affective mimetic responses of male Wistar rats with prior access to 6% ethanol in their home cages were observed during intraoral infusions of an equivalent alcohol solution. Ethanol preference in the home cage appeared unrelated to measures of aversion and ingestion in the taste reactivity tests in normal rats. Adrenalectomy, which significantly reduced home cage ethanol preference, failed to influence the taste reactions elicited by ethanol or water. On the other hand, treatment of intact rats with the 5-HT1A receptor agonist ipsapirone (2.5 mg/kg), a drug that also decreases ethanol drinking in two-bottle intake tests, did increase the duration of aversive groomings, whereas measures of ingestion remained unaffected. These results suggest that ipsapirone, but not adrenalectomy, may alter the palatability of ethanol; this perceptual change may partly underlie the ability of ipsapirone to reduce home cage alcohol drinking in the rat.

Adrenalectomy↗
PubMedDate not supplied

Effects of ibotenic acid lesions of the ventral striatum and the medial prefrontal cortex on ethanol consumption in the rat.

The purpose of this study was to to assess the effect on ethanol drinking of ibotenic acid lesions in the medial prefrontal cortex and the ventral striatum of female rats with continuous access to water and a 6% ethanol solution. Ibotenic acid infusions in the prefrontal cortex did not affect ethanol intake at any time, but a significant increase in water intake was observed on the third postoperative week. Ventral striatal lesions significantly increased ethanol intake during the first 2 postoperative weeks. On the third week consumption was not significantly different from vehicle-infused controls. Apparently, then, severe excitoxic injury to the ventral striatum is compatible with normal, or increased, intake of ethanol; in contrast, similar lesions reduce the intake of other drugs of abuse such as psychostimulants and opioids.

Alcohol Drinking↗
PubMedDate not supplied

Amphetamine-induced hyperactivity: differences between rats with high or low preference for alcohol.

This study determined the relationship between ethanol intake and spontaneous and amphetamine-induced locomotor activity. Locomotion was studied in high-preferring (HP; > 70% of total fluid intake consumed as alcohol) and low-preferring (LP; < 20% of total fluid intake consumed as alcohol) male Wistar rats with free access to water and a 6% (v/v) ethanol solution for 3 weeks. Following an alcohol-free 3-week period, the animals were tested for spontaneous motor activity for 1 h. One week later, locomotion was recorded in the same activity boxes following a subcutaneous injection with d-amphetamine sulfate (1 mg/kg). For determination of plasma levels of corticosterone, blood samples were taken immediately after each of the two tests for locomotor activity. There was no difference between HP and LP rats with regard to spontaneous locomotor activity. Neither were there any differences in plasma levels of corticosterone between the groups. Amphetamine stimulated locomotion in both HP and LP rats, but to a significantly greater extent in HP animals. Both groups had higher blood levels of corticosterone after the amphetamine test than after the drug-free test, but the corticosterone increase was significantly larger in the HP than in the LP rats. These data indicate that the same neural substrate (e.g., the mesocorticolimbic dopamine system) may mediate important aspects of both ethanol drinking and amphetamine responsiveness. Individual differences in the properties of this substrate may account for the finding that ethanol drinking and amphetamine responsiveness covary. A possible explanation for this association may be that prior consumption of ethanol sensitizes the neural substrate responsible for amphetamine-induced hyperactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMedDate not supplied

Effects of early weaning and social isolation on subsequent alcohol intake in rats.

The present study investigated the influence of early weaning and separation from mother and littermates on voluntary ethanol intake and general activity during prepuberal age, and adult age corticosterone levels. On day 16 after birth the male offspring of a litter were divided in three groups, each subjected to a different rearing condition: 1)early weaned and isolated from its littermates; 2) early weaned but growing up together with two littermates; 3) staying with mother and two littermates. On day 25 the animals were tested for general activity including assessment of fearfulness. From day 30 all animals were given a free choice between water and ethanol solution. The ethanol concentration was increased by 2% during each of the following weeks until 10% was reached during the 5th week. Ten days later, after cessation of alcohol testing, blood samples were taken from the tail for assessment of plasma levels corticosterone. The isolated, early weaning pups displayed higher activity levels than both normally reared pups and group-living, early weaning pups. The quotient peripheral locomotion/total locomotion was lower for the isolated pups compared with the other groups, suggesting less fearfulness in the early weaned, isolated pups. For 2%, 4%, and 6% ethanol solutions the normal-reared rats consumed more ethanol and displayed higher ethanol preference than either of the early weaned groups of animals. No group differences were observed either at 8% or 10% ethanol solutions. Levels of plasma corticosterone in adult age in the early weaned rats were slightly reduced, not reaching statistical significance, compared to the normally weaned animals.

Aging↗
PubMedDate not supplied

Mental well-being in alcohol withdrawal: relationship to alpha2-adrenoceptor function.

The possible relationship between postsynaptic alpha2-adrenoceptor function, as assessed by the growth hormone (GH) response to clonidine (CLON) and aspects of mental well-being by self-report of mood using the Swedish Mood Adjective Check List, was investigated in alcohol-dependent patients in the early withdrawal period. Patients had blunted GH responses to CLON and worse mental well-being than control subjects immediately after the end of alcohol intake. No relation was found between mental well-being and postsynaptic alpha2-adrenoceptor function. After 1 week, the GH responses to CLON remained blunted, whereas the state of mental well-being had improved to levels similar to those of control subjects. The results further support a downregulated alpha2-adrenoceptor function during 1 week of alcohol withdrawal. Furthermore, even if subsensitive postsynaptic alpha2-adrenoceptor function was not generally related to state of mood, patients with the lowest postsynaptic alpha2-adrenoceptor function reported the highest levels in the dimensions pleasantness/unpleasantness and activation/deactivation when sober.

Adrenergic Agonists↗
PubMedDate not supplied

Psychopathology in alcohol withdrawal: relationship to alpha2-adrenoceptor function.

The possible relationship between postsynaptic alpha2-adrenoceptor function, as assessed by growth hormone (GH) response to clonidine (CLON; 1.5 or 2.0 microg/kg i.v.), and psychopathology was investigated in 30 patients with alcohol-dependence in the early withdrawal period. Excluding patients with high baseline GH, 23 of the 26 patients had blunted GH responses to CLON and 57% moderate or severe depression at day 1 after the end of alcohol intake. After 1 week, the GH responses to CLON remained blunted in 20 of 21 retested patients, whereas the depression and anxiety remitted in all but two patients. The results do not support any relationship between postsynaptic alpha2-adrenoceptor function and symptoms of psychopathology in alcohol withdrawal.

Adrenergic Agonists↗
PubMedDate not supplied

Effect of local intracerebral corticosterone implants on alcohol intake in the rat.

Corticosterone acts within the brain to stimulate alcohol consumption in the rat. The experiments reported here were aimed at identifying where in the brain corticosterone acts to facilitate ethanol drinking. The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a 1-week pre-operative baseline period and following implantation of corticosterone in various brain areas. Animals bearing unilateral or bilateral implants of corticosterone in the ventral striatum showed increased ethanol consumption compared to cholesterol-treated controls. Ethanol intake was not affected when corticosterone was implanted into septum, hippocampus, or thalamus. Neither were changes in fluid intake detected in animals bearing ventral striatal implants of two related steroid hormones, aldosterone and testosterone. These results indicate that corticosterone partly acts within the ventral striatopallidal system to facilitate alcohol consumption in the rat.

Alcohol Drinking↗