Regulation and possible physiological role of the Ca2-dependent K+ channel of cortical collecting ducts of the rat

In the luminal membrane of rat cortical collecting duct (CCD) a big Ca²⁺-dependent and a small Ca²⁺-independent K⁺ channel have been described. Whereas the latter most likely is responsible for the K⁺ secretion in this nephron segment, the function of the large-conductance K⁺ channel is unknown. The regulation of this channel and its possible physiological role were examined with the conventional cell-free and the cell-attached nystatin patch-clamp techniques. Patch-clamp recordings were obtained from the luminal membrane of isolated perfused CCD segments and from freshly isolated CCD cells. Intracellular calcium was measured using the calcium-sensitive dye fura-2. The large-conductance K⁺ channel was strongly voltage- and calcium-dependent. At 3 mol/l cytosolic Ca²⁺ activity it was half-maximally activated. At 1 mmol/l it was neither regulated by cytosolic pH nor by ATP. At 1 mol/l Ca²⁺ activity the open probability (P _o) of this channel was pH-dependent. At pH 7.0 P _o was decreased to 4±2% (n=9) and at pH 8.5 it was increased to 425±52% (n=9) of the control. At this low Ca²⁺ activity the P _o of the channel was reduced by 1 mmol/l ATP to 8±4% (n=6). Cell swelling activated the large-conductance K⁺ channel (n=14) and hyperpolarized the membrane potential of the cells by 9±1 mV (n=23). Intracellular Ca²⁺ activity increased after hypotonic stress. This increase depended on the extracellular Ca²⁺ activity. A possible physiological function of the large-conductance K⁺ channel in rat CCD cells may be the reduction of the intracellular K⁺ concentration after cell swelling. Once this channel is activated by increases in the cytosolic Ca²⁺ activity it can be regulated by changes in cellular pH and ATP.Supported by DFG Schl 277/2-3     

Temporal relationship between noradrenaline release in the central amygdala and plasma noradrenaline secretion in rats and tree shrews

In pentobarbital anesthetized Wistar rats and tree shrews (Tupaia belangeri) the hypothalamus, the hippocampus and the amygdala were simultaneously superfused through push-pull cannulae with artificial cerebrospinal fluid. Blood samples were withdrawn in order to make an attempt to correlate release rates of noradrenaline (NA), adrenaline and dopamine in the above-mentioned areas with plasma catecholamine levels. A strong, positive correlation was found between NA release in central amygdala and NA concentrations in peripheral blood suggesting a functional relationship between noradrenergic systems in discrete brain areas and the activity of the peripheral sympathetic nervous system.     

Psychiatric comorbidity of smoking and nicotine dependence

Recent epidemiologic studies have revealed that comorbidity of psychiatric disorders is far more pervasive than previously suspected. Strong associations have been reported between specific substance use disorders and between any mental disorder and any substance use disorder. This report focuses on comorbidity of nicotine dependence, a substance use disorder on which little epidemiologic information is available. Data come from an epidemiologic study of approximately 1000 young adults in southeast Michigan, in which the NIMH-DIS, revised according to DSM-III-R, was used. Lifetime prevalence of nicotine dependence was 20%. Males and females with nicotine dependence had increased odds for alcohol and illicit drug disorders, major depression, and anxiety disorders, compared with nondependent smokers and nonsmokers combined. Major depression and any anxiety disorder were associated specifically with nicotine dependence. Increased odds for alcohol or illicit drug disorders were observed also in nondependent smokers, compared to nonsmokers. History of early conduct problems increased the odds for nicotine dependence among smokers. Potential mechanisms in the comorbidity of nicotine dependence are discussed.     

湖南省两地区成瘾物质使用状况调查报告：使用率及相关因素

本文采用整群抽样的方法，对湖南两地区城乡共２３７７人（１５岁以上）的成瘾物质使用状况进行调查，其中男１１７９（４９．６％）人，女１１９９（５０．４％人），平均年龄男女分别为４１．２（ＳＤ＝１７．５）和４３．４（ＳＤ＝１８．６）。结果表明，饮酒率男性为５７．５％，女性为１７．３％，吸烟率男女分别为６８．２％和１１．７％；饮酒者多集中在每月饮１次左右的人群中（男５７．９％，女７７．９％），但吸烟者多集中在每日吸２０支及以上（男５２．４％，女４２．９％）的人群中。除解热镇痛剂外，男性各种精神活性物质的使用频率及剂量皆男高于女性，开始使用的年龄及成瘾的年龄男性低于女性；性别、使用频度、最早使用的年龄、婚姻与饮酒、吸烟量关系最为密切。有１４人使用过鸦片类物质，４人使用过兴奋剂。作者讨论了我国成瘾物质使用的特点，指出经济水平、社会文化背景等因素与我国社会性成瘾物质的使用有密切关系。     

Effect of μ-Opiate Receptor Agonist Tetrapeptide A10 on DNA Synthesis and Protein Content in the Myocardium of Albino Rats

Effect of intraperitoneal injection of tetrapeptide A10 (H-Tyr-D-Orn-Phe-Gly-OH), selective -opiate receptor agonist, synthetic analog of dermorphine, in a dose of 100 g/kg on DNA synthesis and protein content in the myocardium was studied in albino rats. Five injections of tetrapeptide on days 2-6 after birth caused no changes in DNA synthesis 17 days after the last injection, i. e. in 24-day rats. The number of nucleoli and their area increased. In adult males long-term (3-week) treatment with tetrapeptide A10 increased the number of nucleoli and the mean and integral optical density of isolated cardiomyocytes stained with amido black B, which probably attested to activation of protein synthesis in the myocardium. Simultaneously, the content of catecholamines in the heart increased. These data are comparable with delayed effects of k-opiate receptor agonist dinorphine A1-13 and indicate that morphogenetic properties of opioid peptides in rat myocardium are realized via the same routes.     

Gradual potentiation of isometric muscle force during constant electrical stimulation

An investigation was carried out into how stimulation frequency and stimulation history affect the potentiation of muscle force during 20s of constant stimulation of the two knee extensors in isometric conditions. Stimulation frequency significantly affected the potentiation pattern: low-frequency (2.5–10 Hz) stimulation showed a reduction and subsequent enhancement of force, and high-frequency (14.3–25 Hz) stimulation showed only enhancement of force. The degree of enhancement in force and time-to-peak decreased with the stimulation frequency. Whereas conditioning stimulation (both 40 Hz and 14.3 Hz) significantly enhanced the muscle force above 85%, following main stimulation (14.3 Hz) after short rest (10 s and 50 s, respectively) induced little force enhancement (below 8%). In particular, when the frequency of the conditioning stimulation was 14.3 Hz, the initial force at the main stimulation showed a very similar value to the final force value of the conditioning stimulation (above 90% similarity). The potentiated twitch force slowly decayed during rest, with an average time constant of 2.4 min. These observations indicate that muscle potentiation depends on the stimulation frequency and stimulation history, and therefore a computer model of potentiation can play an important role in predicting muscle force and body movement induced by electrical stimulation.     

Adaptive changes in cerebral blood flow and oxygen consumption during ethanol intoxication in the rat

Cerebral blood flow (CBF) and oxygen consumption (CMRO₂) were measured during acute and long-term ethanol intoxication in the rat. The purpose was to investigate whether the adaptive changes (development of tolerance) occurring in the CNS during ethanol intoxication were associated with changes in CBF and/or CMRO₂. Consistent with other studies we found that acute severe ethanol intoxication (median blood alcohol concentration (BAC=5.4 mg/ml)) caused a significant decrease in CBF and CMRO₂. After 3–4 days of severe intoxication (BAC of 6.6 mg/ml) these physiological variables were less affected indicating that functional tolerance had developed: CMRO₂ and CBF during acute ethanol intoxication were 9.3 ml/100 g/min and 60 ml/100 g/min respectively; after the long term intoxication period these variables reached 11.2 ml/100 g/min and 78 ml/100 g/min respectively, i.e. values not significantly lower than those of the control group. After induction of hypercapnia (PaCO₂ about 80 mmHg) CBF increased by 360% in the control group; in the acutely intoxicated group CBF increased by only 127% and in the long term intoxicated group by 203 % indicating that the cerebrovascular CO₂-reactivity had also adapted to the ethanol intoxication. It is concluded that adaptive changes of the CNS to chronic ethanol intoxication comprise alterations in CMRO₂, CBF and cerebrovascular reactivity.     

Ampullary electroreceptors in catfish (Teleostei): temperature dependence of stimulus transduction

The response properties of ampullary electroreceptors have been studied in the catfish Ictalurus nebulosus at skin temperatures between 5 and 35 °C. A unimodal relationship between spontaneous activity and temperature was obtained. Mean (±SEM) peak discharge rate was 57.3 ±1.8 impulses s^–1 at 25 ° C; the receptors were active at 5 °C (15.0 impulses s^–1) and at 35 °C (31.5 impulses s^–1). There were no dynamic responses to temperature changes in either the warming or cooling direction. The shape of the frequency characteristic depended on temperature: the peak of the gain curve shifted to low frequencies at low temperatures. There was a concomitant change of the phase characteristic: the intersection at zero degree phase angle shifted to higher frequencies with an increase of temperature, thus increasing the lead at lower frequencies and decreasing the lag at higher frequencies. Latency after combined excitatory and inhibitory impulse stimulation was temperature dependent, ranging from 16.4 ms (5 °C) to 5.6 ms (35 °C). Application of the specific calcium channel blocker menthol (0.2 mM) suppressed spontaneous activity, the effect becoming more prominent at higher temperatures. Sensitivity to sinusoidal electrical stimulation was also impaired, but to a lesser degree and mainly at lower temperatures. We conclude that the filter properties of the receptor organ can be modelled by a band-pass filter in series with a latency, both of which are temperature dependent. These filter properties might be partially based on the activation kinetics of the tranduction channels.     

The dependence of the latency relaxation on temperature in single muscle fibres of the frog

The time course of the latency relaxation was studied at various temperatures in the range 0–26°C. Over the entire range the time of onset of the drop in tension, t₁, was independent of sarcomere length. At temperatures above 12–15°C the falling phase had a point of inflexion, while at lower temperatures there was an interval during which the tension fell at a constante rate. The time when the rate of drop in tension had passed its maximum value t_1,2, the time to the maximurn drop in tension t₂, and the time when the tension crossed the resting level t₃, all showed linear dependence on sarcomere length in the range from 2.1 to 2.7–3.4 μm. In this range the durations of the intervals t_1.2-t₁, t₂-t₁, and t₃-t₁ were nearly proportional to the distance from the Z-line to the end of the zone of overlap between the thick and the thin filaments. This could be explained as the activation being a longitudinal process starting from the Z-line. The slopes (dt/dS) of the linear portions of the time variables t_1,2, t₂, and t₃ in a time-sarcomere length (S) diagram all had the same dependence on temperature giving a Q₁₀ of 1.75. Under the assumption that the activation process followed a diffusion of calcium from the Z-line region to the zone of overlap a diffusion coefficient was estimated. At room temperature it had a magnitude of about 1/20 of that for calcium chloride in water. It had a dependence on temperature corresponding to an Arrhenius activation energy of about 37 kJ/mol which is about twice the activation energy for a simple diffusion of calcium in water. The results can be interpreted in terms of the time course of the latency relaxation mainly reflecting a longitudinal diffusion of calcium ions in the sarcoplasm.     

Opioid dependence prevents the action of pertussis toxin in the guinea-pig myenteric plexus

Summary The longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum has been employed for the study of the effect of pertussis toxin (IAP) on opioid dependence. Guinea-pigs were treated with IAP (120 g/kg, i.p.) either prior to chronic administration of an opioid or after opioid dependence had been established. The isolated preparations were tested in vitro for dependence; that is, the naloxone-precipitated withdrawal contracture. Naloxone almost failed to evoke a sign of dependence in preparations treated with IAP prior to chronic exposure to an opioid. In contrast, IAP failed to affect the withdrawal contracture when applied to an animal after dependence has been established. It is concluded that theN _i-unit, the substrate for IAP, plays a critical function in the development of dependence. The continuous activation of the opioid receptor associated with the development of dependence may induce changes inN _i which in turn prevent the interaction of IAP with its substrate.