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11.
12.
Tracy Brightman Jiang-Hong Ye Elizabeth Ortiz-Jimenez Edward J. Flynn Wen-Hsien Wu Joseph J. McArdle 《Brain research》1995,678(1-2)
While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM–0.001 μM) potentiatedIGABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect onIGABA. Finally, when 0.001 μM BDM, 10–30 μM PTX and GABA were co-applied the inhibitory effect of the toxin onIGABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA. 相似文献
13.
U. Ravens Michael O. Flüß Q. Li Herbert M. Himmel Erich Wettwer Michael Klockow Inge Lues 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(6):733-742
The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(1-(α-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4- tetrahydroquinoline-6-yl)-6-methyl-3,6-dihydro-2H-1,3,4
-thiadiazine-2-on) is a Ca2+-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological
effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca2+-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 μM) shifted the EC50 of Ca2+ for contractile activation of skinned fibers of pig heart from 2.41 μM to 0.73 μM, whereas [-]-EMD 60264 (30 μM) was ineffective.
In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative
inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure.
The maximum increase in force of human atrial trabeculae was 35 % of pre-drug control with [+]-EMD 60263 in comparison to
113 % with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however,
both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly
activating component IKr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling
the effects of the antiarrhythmic agent E-4031 which had been originally used to define IKr. It is concluded, that the positive inotropic action of [+]-EMD 60263 can be explained by prevalence of the Ca2+-sensitizing effect. The accompanying prolongation in action potential duration is caused by block of the IKr component of the delayed rectifier. While the inotropic effects are stereoselective, most of the electrophysiological actions
are clearly independent of sterical configuration. The combination of Ca2+-sensitizing with class-III antiarrhythmic action may provide an interesting pharmacological profile of potential therapeutic
use.
Received: 7 January 1997 / Accepted: 25 February 1997 相似文献
14.
Min Zong Xinchun Yang Xiulan Liu Liang Shi Taifeng Liu 《岭南心血管病杂志(英文版)》2007,8(4):187-193
Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current (INa-Ca) and late INa in M region (deep subepicardial to midmyocardial). Studies from our laboratory have found a new repolarization current-nonselective cation current (NSCCs) existing in rabbit right ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp techniques. The permeability to Na , K , Li , Cs but not to Cl- indicating that it was a nonselective cation current. Gd3 (0.1 mmol/l) and La3 (0.1 mmol/l) can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -80 mV, INs current density was (-0.44±0.05) PA/PF in endocardial cells, (-0.12±0.05) PA/PF in M cells and (-0.28±0.07) PA/PF in epicardial cells; and with repolarization to 30 mV, INs current density was (1.09±0.29) PA/PF in endocardial cells, (0.38±0.09) PA/PF in M cells and (0.91±0.32) PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias. 相似文献
15.
根据微动滑移振幅具有小位移的特点,设计制作了一种弓形传感装置,该装置能把小幅位移信号转换为电信号,并通过示波器实时显示出来,用这种测试装置来测量滑移式微动振幅具有测试方法简单而测试精度较高的优点。 相似文献
16.
Stefan I McDonough 《Toxicon》2007,49(2):202-212
Some of the most potent and specific inhibitors of voltage-gated calcium channels are peptide toxins that inhibit channel function not by occlusion of the channel pore, but rather by interfering with the voltage dependence and kinetics of channel opening and closing. Many such gating modifier toxins conform to the inhibitor cystine knot structural family and have primary sequence or functional mechanism similar to toxins that target voltage-gated sodium or potassium channels. This review introduces known gating modifiers of calcium channels, discusses the selectivity, binding sites, and mechanism of the toxin-channel interaction, and reviews the usefulness of these toxins as research tools and as the basis for novel calcium channel pharmacology and therapeutics. 相似文献
17.
R. Lemmens-Gruber H. Marei P. Heistracher 《Naunyn-Schmiedeberg's archives of pharmacology》1997,355(2):230-238
GE 68 ((Rac.)-1-[3-(Phenylethyl)-2-benzofuryl]-2-(propylamino)-ethanol hydrochloride) is structurally related to propafenone,
and exerts negative inotropic and negative chronotropic effects similar to the parent drug, but lacks any β-adrenoceptor blocking
activity contrary to propafenone. Thus, the electrophysiological effects of GE 68 were studied in papillary muscles, left
atria, Purkinje fibres, sinoatrial nodes and ventricular myocytes of the guinea-pig heart with the intracellular microelectrode
technique and the patch-clamp technique in the cell-attached mode.
The decrease of the maximum upstroke velocity (V˙max) by GE 68 (1 to 10 μM) was use- and frequency-dependent. V˙max recovered from the use-dependent block with a time constant of 4.1 ± 0.6 s. In papillary muscles and Purkinje fibres action
potential duration was shortened, while it was prolonged in left atria and sinoatrial nodes. Half-maximal steady-state inactivation
of the sodium channels was shifted to more negative membrane potentials (control: –91.5 ± 0.8 mV, 10 μM GE 68: –97.9 ± 2.5 mV).
The peak of the current-voltage relationship and the reversal potential were not changed by GE 68. The amplitude of the unitary
current remained unaltered, while open state probability was decreased. The most striking effect of GE 68 was an increase
of the number of sweeps without single channel openings (1 μM: 2 fold, 10 μM: 6 fold). GE 68 also caused a decrease of the
mean open times, and an increase of the mean closed times in unmodified and pronase-modified sodium channels.
Besides the lack of β-adrenoceptor blocking activity, data present a faster recovery from the use-dependent block by GE 68
and a lower affinity to inactivated sodium channels compared to the reference drug propafenone, as well as differences in
the effect on single channel kinetics.
Received: 25 July 1996 / Accepted: 14 October 1996 相似文献
18.
Kim C. Donaghue M.M. Pena A.T.W. Fung M. Bonney N.J. Howard M. Silink J. Schwingshandl 《Diabetic medicine》1995,12(10):868-873
The study aimed to compare the longitudinal assessment of autonomic nerve function by computerized infrared pupillometry and standard cardiovascular tests in adolescents with diabetes. Adolescents (n = 150) were assessed at two time points (T1 and T2). The median time interval between assessments was 1.5 (range 0.9–3) years. At T1 the median age was 14.5 (range 8.3–19.5) years and the median duration was 6.5 (range 1.1–16) years. The pupillary variables assessed included the resting pupil diameter, the maximum constriction velocity, and the reflex amplitude of constriction. Heart rate reflexes were assessed in response to deep breathing, the Valsalva manoeuvre, and on standing from a lying position (30/15 ratio). Between visits there was a significant decrease in maximum constriction velocity (6.0 mm s?1 vs 6.3 mm s?1, p = 0.0001) and resting pupil diameter (6.2 mm vs 6.3 mm, p = 0.001). At reassessment pupillary abnormalities increased from 32 (21 %) to 45 (30%), with 17 (54 %) of the initial abnormalities persisting. Adolescents with abnormally slow maximum constriction velocity compared to those with normal maximum constriction velocity had a higher glycated haemoglobin (HbA1c%) at T2 (p = 0.02) and between assessments (p = 0.01). Cardiovascular test abnormalities did not increase between visits and the persistence of initial abnormalities was low (21 %). In summary, pupillometry appears a more sensitive test of autonomic nerve dysfunction in adolescents with diabetes than assessment of cardiovascular reflexes. 相似文献
19.
常规PID控制具有结构简单、稳定性好、可靠性高等优点,在调速系统中被广泛应用。但常规PID控制的设计需依靠数学模型,负载、模型参数的变化及非线性因素等影响常规PID的精确调节。单神经元PSD控制器利用神经元的自学习、自组织能力,根据被控对象的变化情况对控制器的权值进行在线调整,达到在线调整PID参数的目的,并且采用无需对象模型的控制算法构成了自适应控制。与常规的PID调节器相比,具有更好的鲁棒性。同时,通过对PSD控制器的改进,在直流伺服系统的仿真应用中得到了较理想的结果。 相似文献
20.
The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca2+ currents (LVA and HVA ICa, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA ICa in a concentration-dependent manner with a threshold concentration of 10−7 M when the LVA ICa was elicited every 30 s in the external solution with 10 mM Ca2+. The concentration for half-maximum inhibition (IC50) was 1.9 × 10−6M. At 10−5 M or more of KB-2796, a complete suppression of the LVA ICa was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca2+ channel for LVA ICa voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca2+ channel. KB-2796 at a concentration of3.0 × 10−6M also decreased the peak amplitude of the HVA ICa without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10−6M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca2+ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage. 相似文献