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1.
In a partially depolarized guinea pig papillary muscle preparation, BAY K8644 stimulated voltage-operated calcium channels, promoting slow action potentials; this effect was dose-dependent over a concentration range of 3 X 10(-7) M to 3 X 10(-6) M. Isoproterenol and histamine also induced slow action potentials by stimulating beta or H2 receptors, respectively. PK 11195, the antagonist of peripheral type benzodiazepine receptors, inhibited the effect of BAY K8644, but not those of histamine or isoproterenol. Moreover, PK 11195 "dose-dependently" antagonized the ability of RO5-4864 to inhibit the slow action potentials elicited by barium chloride. Thus, in the heart, PK 11195, an antagonist of peripheral type benzodiazepine receptors, can modulate voltage-operated calcium channels when they are activated directly, but not when they are activated by stimulation of neurotransmitter receptors.  相似文献   

2.
The present study reports a discrepancy between the effects of vanadate on the membrane Na+-K+-ATPase and the Na+/K+ pump of the skeletal muscle. Vanadate in concentration 4 X 10(-6) mol/l which is necessary to block the enzyme Na+-K+-ATPase activity of membrane fractions failed to inhibit the electrogenic Na+/K+ pump of intact muscle cells. The effect of vanadate on the electrophysiological parameters of the muscle fibre membrane required much higher vanadate levels, but again, Na+/K+ pump was still active. Vanadate in concentrations 4 X 10(-4) and 4 X 10(-5) mol/l depolarized the membrane potential and decreased the membrane resistance [apparently in consequence of enhanced passive membrane permeability for Na+ ions]. Action potentials and the electrical excitability of the muscle fibre membrane were reduced by these vanadate concentrations.  相似文献   

3.
Electrical and contractile activities of smooth muscle strips isolated from the circular muscle layer of cat gastric antrum were studied using the sucrose gap technique. Bombesin (10(-8) mol/l) depolarized the gastric muscle; this was accompanied by an increase in the strip tone, in the plateau action potential frequency and in both the frequency and the amplitude of the spike potentials as well as by a shortening of the plateau action potential duration. Both the frequency and the amplitude of the phasic contractions increased thereafter. The changes in the frequency of the plateau action potentials and contractions were not influenced either by antagonists of cholinergic and adrenergic receptors or by TTX. In the presence of the Ca antagonists D600 (10(-6) mol/l) and nifedipine (10(-7) mol/l) or in Ca-free medium containing EGTA the effect of bombesin on the frequency of the plateau action potentials and phasic contractions remained unchanged; however, spike potentials were not observed and no increase in the amplitude of phasic contractions occurred. UV-light inactivation of nifedipine restored the typical bombesin effect on the electrical and contractile activities of the gastric smooth muscle. The present data suggest that the effect of bombesin on the frequency of both plateau action potentials and phasic contractions is not linked with Ca2+ influx.  相似文献   

4.
The electrophysiological effects of bromobenzoyl - methyladamantylamine ( BMA ) were investigated in isolated electrically driven right ventricular papillary muscles of guinea pigs using conventional glass-microelectrode technique. BMA markedly increased the action potential duration, depolarized the membrane, reduced the maximum rate of depolarization (Vmax) and induced pacemaker-like action potentials. In ventricular myocardium depolarized partially (up to --40 mV) by incubation with 26 mM K+-Krebs solution, BMA induced slow action potentials. In these preparations, BMA was also able to evoke automaticity. Since the pacemaker activity occurring in the voltage range of --90 mV to --60 mV has been attributed to the deactivation of a pacemaker K+ current labelled IK2, and that occurring in the plateau range (from --40 mV to +10 mV) has been attributed to the deactivation of an outward plateau K+ current labelled IX1 , it can be concluded that BMA may inhibit both IK2 and IX1 currents.  相似文献   

5.
In isolated papillary muscles of guinea pigs, the influence of isoproterenol, histamine, theophylline, and phenylephrine on the maximal rate of rise (Vmax) of Na+-dependent action potentials and on isometric contractile force was studied under rested state conditions. Isoproterenol (1 x 10(-7) mol/L), histamine (2 x 10(-5) mol/L), and theophylline (2 x 10(-3) mol/L) shifted the voltage dependence of Vmax into the hyperpolarizing direction and, consequently, led to a voltage-dependent Vmax blockade. The alpha-adrenoceptor agonist phenylephrine, on the other hand, proved to be ineffective in depressing Vmax. The beta-receptor blocker pindolol (4 x 10(-6) mol/L) or the H2-receptor blocker cimetidine (4 x 10(-5) mol/L) abolished the inhibitory effects of isoproterenol and histamine, respectively, and caused Vmax to return to the initial control value. A concentration-response relationship analysis at -65 mV revealed that isoproterenol exerted only a weak inhibitory effect on Vmax compared with its positive inotropic action. The IC50 value of the former effect amounted to approximately 5 x 10(-6) mol/L, but the EC50 value of the latter effect was 4 x 10(-8) mol/L. It is, therefore, concluded that, in physiologically relevant concentrations, beta-adrenergic agonists are unlikely to significantly modulate Na+-dependent excitability even in partially depolarized myocardium.  相似文献   

6.
The effects of protein kinase C activation by 12-O-tetra-decanoyl-phorbol-13-acetate (TPA) on the functions of guinea-pig smooth muscle taenia coli have been studied, using double-sucrose-gap method. A 15-20-min treatment of the muscle with 2 X 10(-8) M TPA caused a progressing inhibition of spontaneous electrical activity and mechanical tension, suppression of post-hyperpolarizing electrical and contractile "off-responses", a decrease in the number of action potentials during superthreshold membrane depolarization, depression of electrical and mechanical responses induced by acetylcholine, histamine, bradykinin mediators. The treatment of pre-depolarized (140 mM kappa+) muscle with 2.10(-8) TPA has led to a considerable reduction in contractile responses induced by the above mediators. The results obtained indicate that protein kinase C is capable of regulating both voltage-sensitive and receptor-operated ionic channels in smooth muscle cells.  相似文献   

7.
Trypsin-dispersed cells from hearts (ventricles) of 7 to 8 day chick embryos were cultured 3 to 21 days. The cells became attached to the culture dish and assembled into monolayer communities. By means of a bridge circuit, one microelectrode was used for simultaneously passing current and recording membrane potentials (Vm). The input resistance, calculated by the measured ΔVm for a known step of current, averaged 10 MΩ. Electrotonic depolarization of nonpacemaker cells had no effect on frequency of firing. Within 2 min after addition of Ba++ (5 to 10 mM) to the Tyrode bath, the cells became partially depolarized and quiescent nonpacemaker cells developed oscillations in Vm which led to action potentials. With time, the depolarization became nearly complete and the input resistance increased 2 to 10 times. During such sustained depolarizations, action potentials were no longer produced and often tiny oscillations were observed; however, large action potentials developed during hyperpolarizing pulses. Thus, the automaticity of the depolarized cell became apparent during artificial repolarization. Sr++ (5 to 10 mM) initially produced hyperpolarization and induced automaticity in quiescent nonpacemaker cells. Elevated [K+]o (20 to 30 mM) suppressed automaticity of pacemaker cells and decreased Rm concomitantly. Thus, Ba++ probably converts nonpacemaker cells into pacemaker cells independently of its depolarizing action. Ba++ may induce automaticity and depolarization by decreasing g K, and elevated [K+]o may depress automaticity by increasing g K. The data support the hypothesis that the level of g K determines whether a cell shall function as a pacemaker.  相似文献   

8.
The effects of bromobenzoyl-methyladamantylamine (BMA) on the transmembrane potentials, contractile force, and 42K efflux were investigated and compared to that of isoproterenol (IPR) in guinea pig ventricular myocardium. Both drugs exerted positive inotropic effect. BMA lengthened the action potential duration, depolarized the membrane, and decreased the Vmax. IPR increased the height of the plateau, accelerated repolarization, slightly increased the resting potential. In preparations depolarized partially by 26 mmol/l K+, both BMA (10(-4) mol/l) and IPR (10(-7) mol/l) induced slow response action potentials, but the duration of BMA-induced ones was twice longer than that of IPR-induced ones. BMA markedly reduced the 42K efflux from ventricular myocardium, whereas IPR had no effect on it. Moreover, BMA also decreased the 26 mmol/l K+-induced increment in 42K efflux, while IPR did not. It is concluded that BMA and IPR exert their positive inotropic effects on different ways. IPR increases the slow inward Ca2+ current directly by activating a phosphorylation process, whereas BMA enhances it indirectly by reducing the K+ conductance, lengthening the repolarization and consequently prolonging the time during which the slow inward Ca2+ current can be operative.  相似文献   

9.
The present experiments show that cortisol when applied in vitro, exerted two different effects on the electrical excitability of the diaphragm muscle fibre membrane and on the neuromuscular transmission depending on the concentration used. At low concentrations (2.5X10(-6) mol.l-1) it potentiated action potentials, increased resting membrane polarization by 3--4 mV and did not affect neuromuscular transmission. Higher concentrations (10(-2) mol.l-1) suppressed the action potential to a certain extent, depolarized the muscle fibre membrane by 6 mV and reduced the amplitudes of m.e.p.p.s and e.p.p.s as well as those of iontophoretically evoked acetylcholine potentials. It was concluded that the effect of low concentrations of cortisol is primary and is probably due to the enhancement of resting membrane permeability for K+ ions and to the changes in ion channels. Cortisol in high doses increased muscle oxygen consumption, so that its suppressing effect might be due to inhibition of energy metabolism.  相似文献   

10.
Cardiac transmembrane potentials and Na and Ca currents were recorded at different temperatures in rat and hedgehog ventricular muscle. At 35 degrees C in both species resting potential was about -80 mV and upstroke velocity (Vmax) of the action potential above 100 V/s. The shape of the action potential in hedgehog ventricular cells at 35 degrees C was similar to that in the rat showing a fast repolarization phase. When temperature was decreased, the membrane resting potential depolarized and action potential amplitude and Vmax declined. In rat ventricular cells at 10 degrees C, the resting potential was about -40 to -50 mV and Vmax was reduced to about 5 V/s. In hedgehog ventricular cells, however, the transmembrane potentials and Vmax were better maintained at low temperature. Phase 3 of the action potential was markedly prolonged below 20 degrees C in hedgehog but not in rat ventricular cells. When temperature was decreased to 10 degrees C the availability curve of the Na current shifted toward more negative potentials and ICa.peak declined in rat ventricular cells. In hedgehog cardiac preparations, the Na current was less influenced by the cooling and ICa.peak did not change very much at low temperatures. A transient inward current usually considered to induce cardiac arrhythmias could be recorded in rat ventricular cells below 20 degrees C but not in hedgehog preparations. These features of hedgehog cardiac membranes may contribute to the cold tolerance and the resistance to ventricular fibrillation during the hypothermia in mammalian hibernators.  相似文献   

11.
Summary 1. We report that NG108-15 (neuroblastoma × glioma) cells differentiated in defined serum-free media are capable of exhibiting stable automaticity (the spontaneous occurrence of regenerative action potentials) following exposure to extracellular perfusates containing NH4Cl. 2. Membrane depolarization (4–5 mV) concomitant with an increased pHi during NH4Cl exposure are followed by hyperpolarization (5–7 mV), subthreshold oscillations, and spontaneous firing after the removal of NH4Cl. 3. Cells cultured in 10% serum did not exhibit automaticity. Cells cultured in serum-free media are twice as likely to show automaticity as those cultured in reduced (1.5%) serum media. 4. We have examined factors that contribute to the events following NH4Cl exposure, namely, membrane depolarization and hyperpolarization, subthreshold oscillations, and automaticity. The inward currents activated at more negative potentials and the ionic currents associated with pronounced afterhyperpolarization in NG108-15 cells cultured in serum-free media provide a basis for the repetitive activity in general and automaticity in particular.  相似文献   

12.
心肌α1—肾上腺素受体激动对豚鼠心室乳头肌的影响   总被引:1,自引:0,他引:1  
施琦  张鸿德 《生理学报》1989,41(5):459-469
The alpha-adrenoceptor agonist phenylephrine (5.0 x 10(-6) mol/L) was used to stimulate myocardial alpha-adrenoceptors of the guinea-pig ventricular papillary muscle, and changes of transmembrane action potential and contractile force of the muscle were observed. The alpha 1-adrenoceptor blocker prazosin (5.0 x 10(-7) mol/L) and the alpha 2-adrenoceptor blocker yohimbine (5.0 x 10(-7) mol/L) were used to determine which subtype of alpha-adrenoceptor is responsible for the effects. The beta-adrenoceptor blocker propranolol (1.0 x 10(-6) mol/L) was used throughout the experiment. The results show that the myocardial alpha 1-adrenoceptor stimulation (1) increases the contractile force of the guinea-pig ventricular papillary muscle, (2) prolongs the time to peak contractile force while the duration of relaxation is not altered, (3) prolongs the fast response action potential duration, and (4) increases the maximal rate of depolarization during the phase 0 of the slow response action potential. It is suggested that the electrophysiological and positive inotropic effects of myocardial alpha 1-adrenoceptor stimulation might be due to the activation of the slow inward current and an increase in Ca2+ influx.  相似文献   

13.
In experiments on the isolated strips of Taenia coli of guinea pigs it was shown that compound D-600 depressed the acetylcholine (5-10(-6), histamine (2-10(-6) and bradykinin (10(-5) gl/ml)-induced contractile response of depolarized smooth muscle. Along with depression of the drug-induced response, compound D-600 depressed the "potassium contracture". It is supposed that the mentioned agents activated the inward flow of Ca2+ ions through the membrane, but not the release of these ions from the sarcoplasmic reticulum.  相似文献   

14.
Zhang LP  Wei Y  Song SL  Cheng M  Zhang Y 《生理学报》2011,63(1):48-54
有研究表明白藜芦醇甙(polydatin)具有抗缺血性心律失常作用,但其电生理学机制尚未明了。本研究旨在应用细胞内记录和全细胞膜片钳方法,探讨白藜芦醇甙对大鼠心室乳头状肌动作电位的影响及其离子机制。结果显示:(1)白藜芦醇甙(50和100μmol/L)可剂量依赖性地缩短正常乳头状肌动作电位复极化50%时间(APD50)和90%时间(APD90)(P<0.01)。白藜芦醇甙对正常乳头状肌静息电位(resting potential,RP)、动作电位幅值(amplitude of action potential,APA)、超射值(overshoot,OS)和0期最大上升速度(Vmax)无影响(P>0.05)。(2)对部分去极化的乳头状肌,白藜芦醇甙(50μmol/L)不但缩短APD50和APD90,而且还降低动作电位OS、APA和Vmax(P<0.05)。(3)ATP敏感钾通道阻断剂格列本脲(10μmol/L)可部分阻断白藜芦醇甙(50μmol/L)的电生理效应。(4)一氧化氮合酶抑制剂L-NAME(1 mmol/L)对白藜芦醇甙的上述效应无影响。(5)白藜芦醇甙(25、50、75、100μmol/L)可浓度依...  相似文献   

15.
硫辛酸抗再灌期心律失常与外源性自由基所致动作电...   总被引:2,自引:0,他引:2  
高天礼  黄玉芝 《生理学报》1991,43(2):149-155
By means of Langendorff method the isolated rat heart was perfused with Krebs Henseleit solution. Following ligation of the left descending coronary artery for 10 min the heart was reperfused for 3 min. The incidence of ventricular fibrillation in the reperfusion period was 100%, and the normal sinus rhythm time was shortened to 29 s within 3 min of reperfusion. Administration of lipoic acid (6.8 X 10(-6)-1.7 X 10(-4) mol/L) to the perfusate significantly reduced the incidence of ventricular fibrillation to 33-50% and prolonged the normal sinus rhythm time to 97-107 s. APA, RP, and Vmax recorded from the guinea pig papillary muscle were depressed due to the deleterious effect of xanthine oxidase and hypoxanthine free radical generating system. Under the treatment of lipoic acid (3.5 X 10(-5) mol/L), the depression of APA, RP, and Vmax were significantly relieved. This confirms that lipoic acid treatment, owing to its free radical scavenger effect, is able to protect myocardium from free radical induced electrophysiological abnormalities, and consequently decrease the incidence of malignant arrhythmias.  相似文献   

16.
新生大鼠离体脊髓薄片侧角中间外侧核细胞的电生理特性   总被引:1,自引:0,他引:1  
祝延  马如纯 《生理学报》1989,41(1):63-69
在新生大鼠离体脊髓薄片的中间外侧核作细胞内记录,研究细胞膜的静态与动态电生理特性。细胞的静息电位(RP)变动于-46—-70mV,膜的输入阻抗为108.3±67.9MΩ(X±SD,下同),时间常数9.9±5.6ms,膜电容138.6±124.2pF。用去极化电流进行细胞内刺激时,大部份细胞(85.4%)能产生高频率连续发放,其余细胞(15.6%)仅产生初始单个发放。胞内直接刺激引起的动作电位(AP)幅度为63.4±9.0mV,时程2.4±0.6ms,阈电位水平在RP基础上去极18.7±6.2mV。大部份细胞的锋电位后存在明显的超极化后电位,其幅度为5.1±2.7mV、持续90±31.8ms。刺激背根可在记录细胞引起EPSP或顺向AP,少数细胞尚出现IPSP。而刺激腹根则可引起逆向AP。  相似文献   

17.
The effects of acetylcholine (ACh) were examined on the naturally occurring slow action potentials (APs) of the isolated, organ-cultured, spontaneously beating sinoatrial (SA) node of the rabbit, in the presence or absence of pertussis toxin. The sensitivity of the SA-node preparations to ACh was not altered after 24 h incubation in organ culture medium. Activation of the muscarinic receptor hyperpolarized the cells and reduced the frequency of spontaneous activity at low concentrations (1 X 10(-6) and 3 X 10(-6) M), and completely abolished automaticity at higher concentrations (1 X 10(-5) M). However, stimulated activity was maintained. Increased concentrations (1 X 10(-4) M) of ACh completely abolished excitability. When the SA-node preparations were cultured in the presence of 0.5 micrograms/mL pertussis toxin, concentrations of ACh as high as 1 X 10(-4) M had no effect on the AP parameters and frequency of spontaneous activity. The results indicate that inactivation of G proteins by pertussis toxin caused inhibition of the ACh effects on the automaticity of the SA node. In addition, the blocking effect of ACh to the naturally occurring slow APs was also inhibited by pertussis toxin. We conclude that in the rabbit SA node, the effects of ACh on automaticity and on the slow channels are mediated by G protein.  相似文献   

18.
The effect of Bay K 8644 on the electrical activity of the smooth muscle cells in the main pulmonary artery of the rabbit was examined. In normal physiological solution, the resting membrane potential was -56 +/- 0.6 mV, and the cells were electrically quiescent. Tetraethylammonium (5 mM) depolarized the membrane to about -45 mV, and electrical stimulation elicited action potentials. To suppress contractile responses and thereby facilitate sustained impalements, the muscle strips were bathed with a hypertonic solution containing sucrose. The mean amplitude of the tetraethylammonium-induced action potentials in the hypertonic solution was 35 +/- 0.9 mV. The action potentials were dependent upon the extracellular Ca2+ concentration and were abolished by diltiazem (10(-6) M). Spontaneous action potentials were occasionally generated in the presence of tetraethylammonium alone and could be induced by the further addition of Ba2+ (0.5 mM). The Ca2+ agonist Bay K 8644 (10(-8) to 10(-6) M) had no effect on the resting membrane potential or excitability in normal solution. However, in the hypertonic solution containing tetraethylammonium, Bay K 8644 caused a further depolarization and oscillatory potential changes, which were not prevented by tetrodotoxin. The oscillations were suppressed or abolished by diltiazem or nilvadipine. Thus, active responses can occur in the normally quiescent smooth muscle cells of the rabbit pulmonary artery when the outward K+ current(s) are suppressed.  相似文献   

19.
The purpose of this study was to investigate the actions of estradiol on spontaneous and evoked action potentials in the isolated longitudinal smooth muscle cells of the pregnant rat. Single cells were obtained by enzymatic digestion from pregnant rat longitudinal myometrium. Action potentials and currents were recorded by whole-cell current-clamp and voltage-clamp methods, respectively. The acute effects of 17beta-estradiol on action potentials and inward and outward currents were investigated. The following results were obtained. The average resting membrane potential of single myometrial cells was -54 mV (n = 40). In many cells, an electrical stimulation evoked a membrane depolarization, and action potentials were superimposed on the depolarization. In some cells, spontaneous action potentials were observed. Estradiol (30 microM) slightly depolarized the membrane (ca. 5 mV) and attenuated the generation of action potentials by reducing the frequency and amplitude of the spikes. Afterhyperpolarization was also attenuated by estradiol (30 microM). On the other hand, in 5 of 35 cells, estradiol increased the first spike amplitude and action potential duration, while frequency of the spike generation and afterhyperpolarization were inhibited. In voltage-clamped muscle cells, estradiol inhibited both inward and outward currents. Acute inhibition or augmentation of spike generation by estradiol is due to the balance of inhibition of inward and outward currents. Inhibition of both currents also prevented afterhyperpolarization, causing potential-dependent block of Ca spikes.  相似文献   

20.
The effect of 10(-5) mol/l bencyclane on the repetitive electrical activity of muscle membrane was studied with the conventional microelectrode technique. Electrical activity was induced by repetitive stimulation in normal Ringer solution (train) or by a single depolarizing current pulse in the presence of 10(-6) mol/l cevadine (volley). Bencyclane decreased, in a use-dependent manner, the maximum rates of depolarization and repolarization (Vmax+ and Vmax-, resp.) of the action potentials both of the train and the volley. The inhibition of Vmax+ and Vmax- was proportional; however, it was stronger for the volleys than for the trains. The cycle length (mean interspike interval) of the volley was increased by bencyclane; the prolongation was progressive during consecutive cycles. The dissociation of bencyclane from the Na channel was studied by applying trains of different durations with equal pulse numbers. Bencyclane at a higher concentration (5 x 10(-5) mol/l) caused a reversible tonic block: the overshoot potentials, Vmax+ and Vmax- were markedly reduced. The reduction of Vmax- was slightly stronger than that of Vmax+. Slow membrane potential oscillation (SMPO) was evoked by treating the muscle with 10(-4) mol/l of cevadine. The administration of 5 x 10(-6) mol/l bencyclane decreased the frequency of SMPO, while 10(-5) mol/l bencyclane terminated the slow oscillation activity without changing its baseline potential. The present results indicate that bencyclane induces use-dependent inhibition of Na channels in muscle, similarly as do class 1 antiarrhytnmic drugs. Inhibition was observed with both normal and cevadine-modified Na channels.  相似文献   

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