Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels

The differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) single sodium channel currents in rat dorsal root ganglion (DRG) neurons were investigated using the outside-out configuration of patch-clamp technique. Channel conductances were 10.7 and 6.3 pS for TTX-S and TTX-R sodium channels, respectively, at a room temperature of 24–26°C. The single-channel current of TTX-S sodium channels at the test potential of −30 mV was −1.27 ± 0.25 pA, and was not changed after exposure to 10 μM tetramethrin (−1.28 ± 0.23 pA). The open time histogram of TTX-S single-channel currents could be fitted by a single exponential function with a time constant of 1.27 ms. After exposure to 10 μM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 1.36 ms (τ_fast) and 5.73 ms (τ_low). The percentage of contribution of each component to the population was 62% for the fast component representing the normal channels and 38% for the slow component representing the tetramethrin modified channels. The amplitudc of TTX-R single-channel currents was slightly changed from −0.72 ± 0.14 to −0.83 ± 0.07 pA by 10 μM tetramethrin. The open time histogram of TTX-R single-channel currents could be fitted by a single exponential function with a time constant of 1.92 ms. In the presence of 10 μM tetramethrin, the open time histogram could be fitted by the sum of two exponential functions with time constants of 2.07 ms (τ_fast) and 9.75 ms (τ_slow). The percentage of contribution of each component was 15% for the fast, unmodified component and 85% for the slow, modified component. Differential effects of tetramethrin on the open time distribution of single sodium channel currents explains the differential sensitivity of TTX-S and TTX-R sodium channels.     

Mechanism of action of the epileptogenic drug pentylenetetrazol on a cloned neuronal potassium channel

The action of the epileptogenic agent pentylenetetrazol (PTZ) on a cloned potassium channel of the rat brain was studied. The Kv1.1 channel was expressed in oocytes ofXenopus laevis and potassium currents were investigated in outside-out and inside-out membrane patches. The results show that PTZ increased the multi-channel potassium currents at strongly negative potentials and decreased them at potentials positive to −35 mV both in outside-out and inside-out membrane patches. The extent and manner of PTZ action, the concentration dependence as well as the onset and time course of the PTZ effect were the same both in outside-out and inside-out membrane patches. The single-channel potassium currents showed an increase in open probability and frequency of opening and a decrease in close time at −50 mV and vice versa at 0 mV with application of PTZ. The amplitude of single-channel current, the open time and the latency to the first channel opening remained almost unchanged under PTZ. The results indicate that PTZ acts via the cell membrane and influences the membrane-associated part of the potassium channel. Thereby, PTZ accelerates the transition from the inactivated to the open state of the channel at strongly negative potentials and reduces it at slightly negative and positive potentials. This mechanism may be the basis for a gate function which is in favour of the development of epileptic discharges.     

Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case-control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age- and sex-matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C-reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C-reactive protein [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.054-1.237], alanine aminotransferase activity (OR = 1.008, 95% CI 1.002-1.014), serum sodium concentration (OR = 0.877, 95% CI 0.770-0.999) and serum potassium concentration (OR = 0.319, 95% CI 0.124-0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C-reactive protein (OR = 1.159, 95% CI 1.022-1.315) and serum potassium concentration (OR = 0.222, 95% CI 0.052-0.948) met the significant level. Thus, the values for serum C-reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.     

抑制剂对酪氨酸酶影响的初步研究

采用酶动力学及聚丙烯酰胺凝胶电泳方法研究了ＮａＨＳＯ３、ＮａＮ３、ＫＳＣＮ、ＤＤＣ对酪氨酸酶的抑制作用。ＮａＨＳＯ３、ＮａＮ３、ＫＳＣＮ为非竞争性抑制作用，随着抑制剂浓度增加，酶活性逐渐减弱。当ＮａＨＳＯ３、ＮａＮ３、ＫＳＣＮ的浓度分别达到１．２ｍｍｏｌ／Ｌ１２。５ｍｍｏｌ／Ｌ１２．５ｍｍｏｌ／Ｌ时，酶活性的抑制率为１００％、５０％、２４％。ＤＤＣ对酪氨酸酶的抑制作用为竞争性抑制作用，其浓度达４ｍｍｏｌ／Ｌ时，酶活性１００％受到抑制。     

Nicardipine improves motor tics

Calcium channel blockers can act on dopaminergic systems, and some reports suggest that they could be useful for the treatment of several movement disorders. In order to assess the efficacy of nicardipine in tics disorders we performed a prospective open non-controlled study which included 10 previously untreated patients. Our results suggest that nicardipine could be a useful and safe treatment for tics.     

Calcium entry blocker: Treatment in acute pain in cluster headache patients

15 chronic cluster headache patients in whom pain was induced by nitroglycerin received acute intravenous treatment with a calcium entry blocker. At the time of peak pain we noted a sudden decrease after the Verapamil injection. The mechanism by which the calcium entry blocker afforded relief is unlikely to have been vasodilatation in patients whose blood vessels had just been dilated by nitroglycerin. A more probable mechanism is blockade of the release of the pain-inducing neurotransmitters. The vasodilatation phase is not a primary factor in the onset of pain.

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Sommario Sono stati studiati 15 soggetti affetti da Cluster cronica inducendo loro la crisi dolorosa con Trinitrina, trattandoli poi con calcio antagonista (Verapamil) per via endovenosa. Al momento dell'apice del dolore, valutato dal paziente con un analogo visivo, la somministrazione di Verapamil endovena, determina una rapida estinzione del dolore. L'azione efficace del Ca-antagonista non può sicuramente essere rapportata alla vasodilatazione poiché la crisi dolorosa insorge già in una fase di vasodilatazione per l'azione della Trinitina. Il meccanismo d'azione più probabile è il blocco del release di neurotrasmettitori inducenti l'attacco doloroso. Si sottolinea che la vasodilatazione non è il fattore primario dell'induzione del dolore.

     

不同强度噪声所致蜗内直流电位改变及其机制探讨

本实验观察105 dB—125 dB(声压级,SPL)白噪声暴露20min 对豚鼠耳蜗直流电位(EP)的影响.发现随着噪声强度的增加,EP 发生不同形式的改变:115 dB噪声使 P—EP 增大,而125 dB 则使其减小,但各组负 EP(N—EP)变化不大。提示有血管纹功能从代偿性增强到失代偿的变化过程。本文还利用几种钾离子通道阻断剂对EP 改变的通道机制作了探讨。     

西洋参茎叶皂甙单体Rb_3对大鼠血流动力学及单钙通道活动的影响

单体皂甙Ｒｂ３自西洋参茎叶皂甙中提取。Ｒｂ３３０ｍｇ·ｋｇ－１可使麻醉大鼠在体心脏的ＭＡＰ，±ｄＰ／ｄｔｍａｘ和ＬＶＳＰ减少。用斑片钳的连细胞电压钳法证明．Ｒｂ３３００ｍｇ·Ｌ－１使Ｌ、Ｂ、Ｔ型钙通道的开放时间缩短、开放概率减少，其作用与异搏定３７．５ｍｇ·Ｌ－１相似，与ＢａｙＫ８６１１５μｍｏｌ·Ｌ－１作用相反。确切地证明Ｒｂ３对钙通道有阻滞作用。     

硝苯地平对抗吗啡戒断所致焦虑作用研究

目的··：评价钙拮抗剂硝苯地平对戒断后期焦虑症状及复吸的治疗作用。方法··：大鼠自然戒断后，采用Ｖｏｇｅｌ＇ｓ饮水冲突模型（简称Ｖｏｇｅｌ冲突模型）观察吗啡依赖大鼠的焦虑情绪与硝苯地平的作用。结果··：２０，３０，５０ｍｇ·ｋｇ－１的硝苯地平能明显增加大鼠的舔水次数和被电击次数，并呈剂量相关性，以３０ｍｇ·ｋｇ－１作用最为明显。结论··：钙离子拮抗剂可治疗吗啡戒断所致的焦虑症状，可能与５－ＨＴ等神经递质的释放或与ＧＡＢＡ能神经有关     

Role of tyrosine kinase activity in cardiac slow delayed rectifier channel modulation by cell swelling

 We studied the effects of cell swelling on membrane currents of canine ventricular myocytes using the whole-cell patch-clamp method. Cell swelling was induced by lowering the osmolarity of the bath solution to 60% of control. Cell width and currents were measured simultaneously. Cell swelling induced little or no change in the L-type Ca, the inward rectifier, and the transient outward currents, but a marked increase in the slow delayed rectifier current (I _Ks) was seen. We further examined the role of protein kinase activities in I _Ks modulation by cell swelling. This modulation was not affected by inhibiting serine/threonine kinases using H-8. On the other hand, the modulation was inhibited by genistein (a protein tyrosine kinase inhibitor) although not by daidzein (an inactive analogue of genistein). Our data suggest that in canine ventricle cell swelling can increase protein tyrosine kinase activity, which can augment I _Ks and contribute to changes in membrane electrical activity observed under these conditions. Received: 20 September 1996 / Received after revision and accepted: 5 December 1996