共查询到20条相似文献,搜索用时 27 毫秒
1.
I. V. Shemarova S. V. Kuznetsov I. N. Demina V. P. Nesterov 《Journal of Evolutionary Biochemistry and Physiology》2009,45(3):389-399
Earlier we have shown that regulation of rhythm and strength of the frog heart contractions, mediated by transmitters of the autonomic nervous system, is of the Ca2+-dependent character. In the present work, we studied chronoand inotropic effect of verapamil—an inhibitor of Ca2+-channels of the L-type, of nickel chloride-an inhibitor of Ca2+—channels of the T-type and of Na+,Ca2+exchangers as well as of adrenaline and acetylcholine (ACh) after nickel chloride. It has been found that the intracardially administered NiCh2 at a dose of 0.01 μg/kg produced a sharp fall of amplitude of action potential (AP) and an almost twofold deceleration of heart rate (HR). The intracardiac administration of NiCh2 (0.01 μg/kg) on the background of action of verapamil (6 mg/kg, i/m) led as soon as after 3 min to even more prominent HR deceleration and to further fall of the AP amplitude by more than 50% as compared with norm. An intracardiac administration of adrenaline (0.5 mg/kg) partly restored the cardiac activity. However, preservation of the myocardium electrical activity in such animals was brief and its duration did not exceed several minutes. Administration of Ni2+ on the background of acetylcholine (3.6 mg/kg) led to almost complete cessation of cardiac activity. As soon as 3 min after injection of this agent the HR decreased to 2 contractions/min. On electrograms (EG), the 10-fold fall of the AP amplitude was recorded. To elucidate role of extraand intracellular Ca2+ in regulation of strength of heart contractions, isometric contraction of myocardium preparations was studied in response to action of NiCl2 (10–200 μM), verapamil (70 μM), adrenaline (5 μM), and acetylcholine (0.2 μM) after NiCl2. It has been found that Ni2+ causes a dose-dependent increase of the muscle contraction amplitude. Minimal change of the contraction amplitude (on average, by 14.9% as compared with control) was recorded at a Ni2+ concentration of 100 μM. An increase of Ni2+ in the sample to 200 μM increased the cardiac contraction strength, on average, by 41%. The negative inotropic action of verapamil was essentially reduced by 100 μM Ni2+. Adrenaline added to the sample after Ni2+ produced stimulating effect on the cardiac muscle, with an almost twofold rise of the contraction amplitude. ACh (0.2 μM) decreased the cardiac contraction amplitude, on average, by 56.3%, whereas Ni2+ (200 μM) administered after ACh not only restored, but also stimulated partly the myocardial work. Within several parts of percent there was an increase of such isometric contraction parameters as amplitude of the effort developed by muscle, maximal rate, maximal acceleration, time of semirise and semifall. The obtained experimental results indicate that the functional activity of the frog pacemaker and contractile cardiomyocytes is regulated by Ca2+-dependent mechanisms. Structure of these mechanisms includes the potential-controlled Land T-channels of the plasma membrane as well as Na+,Ca2-exchangers characteristic exclusively of contractile cardiomyocytes. The existence of these differences seems to be due to the cardiomyocyte morphological peculiarities that appeared in evolution at the stage of the functional cell specialization. 相似文献
2.
Shemarova IV Kuznetsov SV Demina IN Nesterov VP 《Zhurnal evoliutsionno? biokhimii i fiziologii》2008,44(1):39-50
To elucidate role of intra- and extracellular Ca2+ in regulation of rhythm and strength of frog heart contractions, there were studied ECC and isometric contraction of myocardium preparations in response to verapamil, adrenaline, and blockers of alpha- and beta-adrenoreceptors. It has been shown that after an intramuscular injection of verapamil (6 mg/kg), bradycardia develops, the heart rate (HR) decreasing by 50-70 %. Further, the cardiac arrest occurred; however, administration to the animals of adrenaline (100 mg/kg) restored the cardiac rhythm for a short while. After an intramuscular injection of adrenaline at doses of 0.1-10 mg/kg, no essential changes were observed in the potential action amplitude and HR; an increase of the administered adrenalin concentration to 100 mg/kg was not accompanied by the cardiac rhythm stimulation, as this takes place in homoiothermal animals and human; on the contrary, an essential HR deceleration was revealed. Phentolamine (5 mg/kg) gradually decelerated HR rhythm by 32-45 %. The potential amplitude changed insignificantly. A subsequent intracardiac injection of adrenaline (100 mg/kg) on the background of block of alpha-adrenoreceptors produced acceleration of the rhythm (by 13-21%) and fall of the electrogram amplitude. These results can indicate that in the frog heart, phentolamine interacts predominanty with alpha-adrenoreceptors. An intracardiac administration of propranolol (1 mg/kg) to frogs promoted inhibition of beta-adrenergic receptors and produced a gradual cardiac rhythm deceleration. In experiments on assessment of verapamil effect on the character of contractions this preparation at a concentration of 150 microM was established to produce a significant dosedependent decrease of the contraction strength. A rise of verapamil concentration in the sample to 200 microM led to a decrease of the amplitude, on average, by 68-70 % and in individual preparations -- by 80-85 %; however, administration into the sample of adrenaline (10 microM) restored the cardiac contraction strength. Adrenaline (1 nM--100 microM) increased markedly the contraction amplitude. Phentolamine (10 microM) did not inhibit transmission of contractile signal to cardiomyocytes; this was manifested in that the contraction amplitude after addition of adrenaline (10 microM) into the sample was approximately the same as in the sample containing no phentolamine. Propranolol (10 microM) eliminated the stimulatory action of adrenaline (10 microM). The results of these experiments indicate that in the frog ventricular cardiomyocytes the main adrenaline acceptors are beta-adrenoreceptors. 相似文献
3.
I. V. Shemarova S. M. Korotkov I. N. Demina V. P. Nesterov 《Journal of Evolutionary Biochemistry and Physiology》2010,46(2):167-172
Inotropic effect of Ni2+ on mitochondrial oxidative reactions were studied on myocardium preparations excised from the left frog ventricle and the
rat heart mitochondria (RHM), respectively. In the presence of 10–200 μM Ni2+, the cardiac contraction amplitude increased in the dose-dependent manner. It has been found that Ni2+ is not toxic for RHM. The state 4 by Chance in the KCl medium was stimulated by 100 μM Ni2+. At the same time, Ni2+ did not affect the state 3 and the 2,4-dinitrophenol-stimulated respiration of RHM. Our findings allow suggesting that the
Ni2+-induced increase in the cardiac contraction amplitude is affected by energy state of the rat cardiomyocytic mitochondria. 相似文献
4.
I. V. Shemarova S. V. Kuznetsov I. N. Demina V. P. Nesterov 《Journal of Evolutionary Biochemistry and Physiology》2008,44(6):698-711
To study role of acetylcholine (ACh) in Ca2+-dependent regulation of rhythm and strength of cardiac contractions in the frog Rana temporaria, we studied in parallel experiments the ACh chrono- and inotropic effects on the background of action of blockers of the potential-controlled Ca2+-channels, ryanodine and muscarine receptors. The obtained results indicate participation of acetylcholine in the Ca2+-dependent regulation of the rhythm and strength of the frog cardiac contractions. 相似文献
5.
L-type Ca2+-channel blockers, verapamil (5 μM) and nifedipine (10 μM), have increased the quantum composition of endplate potentials
(EPP) and the level of induced rhythmic activity of neogenic synapses. L-type Ca2+-channel activator BAY K 8644 (1 μM) has a decreased mediator secretion level. Nifedipine (10 μM) has not changed the frequency
and amplitude of diminutive EPPs in the dormant state or during potassium depolarization. Blocking of the prejunctional ryanodine
receptor with ryanodine (10 μM) led to an increase in the single EPP quantum composition that was qualitatively similar to
nifedipine and verapamil, but more marked, and also caused the reinforcement of mediator release during the rhythmic EPP salvo.
Ryanodine receptor activation with ryanodine (1 μM) resulted in reduction of the quantum composition of single and rhythmic
EPPs. This effect was partially prevented with nifedipine (10 μM). 相似文献
6.
The genesis of secondary rhythms in autorhythmic functional systems is analyzed on the example of the spectra of fluctuations of the heart rate observed within early postnatal ontogenesis of rats (from the moment of birth until three weeks old). We studied the effects of blocking of -adrenoreceptors with phentolamine (5 mg/kg, i.p.), of -adrenoreceptors with propranolol (1 mg/kg), and of M cholinoreceptors with atropine (1 mg/kg). We concluded that sympathetic influences stabilize the cardiac rhythm in newborn animals, but from the second postnatal week the effects determining generation of secondary rhythms of cardiac activity begin to be mediated by these receptors. Parasympathetic effects on secondary cardiorhythms mediated by M cholinoreceptors are effective even in newborn rats. In rats older than 7 to 8 days, blocking of -adrenoreceptors and M cholinoreceptors led to the same result, synchronization of the secondary cardiac rhythms. Disorders in the afferent link of the baroreflex arcs after the blockade of -adrenoreceptors and cessation of transmission in the efferent link of these arcs after blockade of M cholinoreceptors are considered a probable reason for this phenomenon. 相似文献
7.
A. V. Krylatov L. N. Maslov S. Yu. Ermakov O. V. Lasukova E. I. Barzakh D. Crawford R. G. Pertwee 《Biology Bulletin》2007,34(1):28-35
Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity of the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since it was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 μM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 μM. 相似文献
8.
Takada M Fujimaki K Hokari S 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2008,178(8):957-962
Adult frog skin transports Na+ from the apical to the basolateral side across the skin. Antidiuretic hormone (ADH) is involved in the regulation of Na+ transport in both mammals and amphibians. We investigated the effect of arginine vasotocin (AVT), the ADH of amphibians,
on the short-circuit current (SCC) across intact skin and on the basolateral Na+/K+-pump current across apically nystatin-permeabilized skin of the tree frog, Hyla japonica, in which the V2-type ADH receptor is expressed in vitro. In intact skin, 1 pM AVT had no effect on the SCC, but 10 nM AVT was sufficient
to stimulate the SCC since 10 nM and 1 μM of AVT increased the SCC 3.2- and 3.4-fold, respectively (P > 0.9). However, in permeabilized skin, AVT (1 μM) decreased the Na+/K+-pump current to 0.79 times vehicle control. Similarly, 500 μM of 8Br-cAMP increased the SCC 3.2-fold, yet 1 mM of 8Br-cAMP
decreased the Na+/K+-pump current to 0.76 times vehicle control. Arachidonic acid (10−5 M) tended to decrease the Na+/K+-pump current. To judge from these in vitro experiments, AVT has the potential to inhibit the basolateral Na+/K+-pump current via the V2-type receptor/cAMP pathway in the skin of the tree frog. 相似文献
9.
Here we describe an experimental design aimed to investigate changes in total cellular levels of Na+ and K+ ions in cultures of freshwater filamentous cyanobacteria. Ion concentrations were measured in whole cells by flame photometry.
Cellular Na+ levels increased exponentially with rising alkalinity, with K+ levels being maximal for optimal growth pH (∼8). At standardized pH conditions, the increase in cellular Na+, as induced by NaCl at 10 mM, was coupled by the two sodium channel-modulating agents lidocaine hydrochloride at 1 μM and
veratridine at 100 μM. Both the channel-blockers amiloride (1 mM) and saxitoxin (1 μM), decreased cell-bound Na+ and K+ levels. Results presented demonstrate the robustness of well-defined channel blockers and channel-activators in the study
of cyanobacterial Na+- K+ fluxes.
Published: June 29, 2004. 相似文献
10.
María G. López Ordieres Georgina Rodríguez de Lores Arnaiz 《Neurochemical research》2009,34(12):2226-2232
Na+, K+-ATPase is inhibited by neurotensin, an effect which involves the peptide high affinity receptor (NTS1). Neurotensin effect
on cerebral cortex synaptosomal membrane Na+, K+-ATPase activity of rats injected i.p. with antipsychotic clozapine was studied. Whereas 3.5 × 10−6 M neurotensin decreased 44% Na+, K+-ATPase activity in the controls, the peptide failed to modify enzyme activity 30 min after a single 3.0, 10.0 and 30.0 mg/kg
clozapine dose. Neurotensin decreased Na+, K+-ATPase activity 40 or 20% 18 h after 3.0 or 5.6 mg/kg clozapine administration, respectively, and lacked inhibitory effect
18 h after 17.8 and 30.0 mg/kg clozapine doses. Results indicated that the clozapine treatment differentially modifies the
further effect of neurotensin on synaptosomal membrane Na+, K+-ATPase activity according to time and dose conditions employed. Taken into account that clozapine blocks the dopaminergic
D2 receptor, findings obtained favor the view of an interplay among neurotensinergic receptor, dopaminergic D2 receptor and
Na+, K+-ATPase at synaptic membranes. 相似文献
11.
I. V. Kubasov R. S. Arutyunyan E. V. Matrosova I. I. Kubasov 《Journal of Evolutionary Biochemistry and Physiology》2016,52(5):369-379
In control experiments (n = 16), during direct stimulation of m. Soleus by trains of 5, 10 and 50 stimuli at a rate of 20 Hz a biphasic change was detected in the amplitude of the last contractile responses (LCRN) depending on N, where N is the number of individual contractile responses in the tetanus. Thus, an initial decrease in LCRN amplitudes (down to 54 ± 8% for LCR5) was followed by a subsequent increase (up to 218 ± 14% for LCR50) and significant shortening of their half-relaxation time compared to the initial response (down to 44 ± 8% for LCR50). Caffeine at concentrations of 5 (n = 6) and 10 (n = 4) mM exacerbated LCR5 depression (down to 31 ± 8% and 15 ± 4%, respectively) against the background of arising characteristic stationary contracture responses. The subsequent increase in the LCRN amplitude was substantially lower than in control experiments (114 ± 18% and 46 ± 9% for LCR50 compared to the initial response at 5 and 10 mM of caffeine, respectively). The LCR50 half-relaxation time during the effect of caffeine at both concentrations also remained considerably shorter than that of individual responses recorded both in the presence of caffeine and in control experiments. In contrast to the control and caffeine effects, LCR5 and LCR10 amplitudes during the effect of 10 μM of dantrolene (n = 5) remained at the level close to that of the first response (102 ± 7% and 106 ± 8%, respectively), while the LCR50 amplitude displayed a considerably smaller increase (to 143 ± 14%) than observed in control muscles. Besides, dantrolene further enhanced muscle relaxation at rest. Caffeine (10 mM), as applied in the presence of dantrolene, restored the dynamics of changes in amplitude–temporal characteristics of last contractile responses to values approximating those in control. The amplitude–temporal characteristics of action potentials recorded extracellularly in individual m. Soleus muscle fibers did not change significantly during the transition from single to train stimulation under the same protocol as in mechanographic experiments. These data may be interpreted in support of the previously advanced hypothesis on the implication of Ca2+-induced Ca2+ release in skeletal muscles under their tetanic stimulation as an additional mechanism of excitation–contraction coupling [1, 2]. 相似文献
12.
Summary Neuropeptide tachykinins, present within sensory nerves, have been implicated as neurotransmitters involved in nonadrenergic and noncholinergic airway muscle contraction. The signal transduction pathways of tachykinins on muscle contraction and Ca2+ mobilization were investigated in swine trachea. Tachykinins, substance P (SP) and neurokinin A (NKA), concentration (1 nM to 1 μM)-dependently induced contractile responses with removal of epithelium, whereas neurokinin B (NKB) did not alter the muscle tension. The SP- and NKA-evoked muscle contractions were inhibited by NK1-R antagonist L732138, but not by either NK2-R antagonist MDL29913 or NK3-R antagonist SB218795. Consistently, SP-elicited increase in [Ca2+]i was abolished by NK1-R antagonist, neither by NK2-R nor NK3-R antagonists. The SP-induced muscular responses were significantly inhibited by L-type Ca2+ channel blocker verapamil and withdrawal of external Ca2+. Caffeine (10 mM) or ryanodine (50 μM) also partly suppressed the SP-induced muscle responses. Inhibition of inositol 1,4,5-trisphosphate (InsP3) receptor with 2-APB (75 μM) potently attenuated SP-evoked Ca2+ mobilization and muscle contraction, which was further inhibited by 2-APB under Ca2+-free external solution, but not completely. Unexpectedly, simultaneous blockade of InsP3 receptor and ryanodine receptor (RyR) by 2-APB and ryanodine enhanced SP-evoked muscle contraction and Ca2+ mobilization. This potentiation was virtually abolished by removal of external Ca2+, suggesting native Ca2+ channels may contribute to this phenomenon. These results demonstrate that tachykinins produce a potent muscle contraction associated with Ca2+ mobilization via tachykinin NK1- R-dependent activation of multiple signal transduction pathways involving Ca2+ influx and release of Ca2+ from InsP3- and ryanodine-sensitive Ca2+ stores. Blockade of both InsP3 receptor and RyR enhances the Ca2+ influx through native Ca2+ channels in plasma membrane, which is crucial to Ca2+ signaling in response to NK1 receptor activation. 相似文献
13.
The plasma membrane calcium ATPases (PMCA) are a family of genes which extrude Ca2+ from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+ signalling, depending on the cell type. In the cardiovascular system, Ca2+ is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction
pathways. A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure
in these systems to maintain normal Ca2+ homeostasis has been linked to both heart failure and hypertension. This article focuses on the functions of PMCA, in particular
isoform 4 (PMCA4), in the heart and vasculature and the reported links between PMCAs and contractile function, cardiac hypertrophy,
cardiac rhythm and sudden cardiac death, and blood pressure control and hypertension. It is becoming clear that this family
of calcium extrusion pumps have essential roles in both cardiovascular health and disease. 相似文献
14.
In the present study, we have investigated the effects of prolonged inhibition of nitric oxide synthase (NOS) by infusion of neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI), to examine modulation of NMDA and GABAA receptor binding in rat brain. The duration of sleeping time was significantly increased by the pre-treatment with 7-NI (100 mg/kg) 30 min before pentobarbital (40 mg/kg) treatment in rats. However, the duration of pentobarbital-induced sleep was shortened by the prolonged infusion of 7-NI into cerebroventricle for 7 days. We have investigated the effect of NOS inhibitor on NMDA and GABAA receptor binding characteristics in discrete areas of brain regions by using autoradiographic techniques. The GABAA receptors were analyzed by quantitative autoradiography using [3H]muscimol and [3H]flunitrazepam binding, and NMDA receptor binding was analyzed by using [3H]MK-801 binding in rat brain slices. Rats were infused with 7-NI (500 pmol/10 l/ h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps. The levels of [3H]muscimol were markedly elevated in cortex, caudate putamen, and thalamus while the levels of [3H]flunitrazepam binding were only elevated in cerebellum by NOS inhibitor. However, there was no change in the level of [3H]MK-801 binding except decreasing in the thalamus. These results show that the prolonged inhibition of NOS by 7-NI-infusion highly elevates [3H]muscimol binding in a region-specific manner and decreases the pentobarbital-induced sleep. 相似文献
15.
Tatiana S. Filatova Nikolay Naumenko Pavel A. Galenko-Yaroshevsky Denis V. Abramochkin 《Journal of physiology and biochemistry》2017,73(2):167-174
Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10?5 M) in the presence of selective M2 antagonist methoctramine (10?7 M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10?8 M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+ currents I to, I Kur, and I Kir. In the absence of M2 blocker methoctramine, pilocarpine (10?5 M) produced stronger attenuation of I CaL and induced an increase in I Kir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10?6 M) and therefore was identified as I KACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of I CaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of I KACh. 相似文献
16.
E. A. Turovskii M. V. Konakov A. V. Berezhnov V. P. Zinchenko G. E. Bronnikov L. P. Dolgacheva 《Cell and Tissue Biology》2011,5(5):511-519
The thermogenic capability of brown adipose tissue is controlled by noradrenaline. By interacting with α1- and β-adrenoreceptors
of adipocytes, noradrenaline (NA) increases the intracellular concentration of Ca2+ ([Ca2+]i) and cAMP. The changes in [Ca2+]i under the action of NA and selective agonists of α1- and β-adrenoreceptors, i.e., cirazoline and isoproterenol (IP), are
recorded on individual cells of the primary culture of adipocytes during the day in vitro (DIV) 1, DIV 3, and DIV 6. The change
in [Ca2+]i under the effect of IP as compared to the response to cirazoline in cells of DIV 1 is characterized by a higher amplitude
and shorter duration of impulses in the entire diapason of the used physiological concentrations. After DIV 3, these differences
are insignificant and, after DIV 6, the differences in kinetics are nearly absent. For all three agonists, the kinetics of
the [Ca2+]i change in the proliferating and differentiated cells is significantly different; i.e., the response amplitude increases with
the age of the culture and the duration of transitory response decreases, while sensitivity to agonists of adrenoreceptors
increases. It can be seen from the rise in [Ca2+]i with an inhibitor of Ca2+-ATPase of the endoplasmic reticulum thapsigargin in calcium-free medium that the source of calcium ions in the endoplasmic
reticulum rises with the growth and development of cells in culture, while the rate at which Ca2+ is pumped out of cells, which characterizes the activity of Ca2+-ATPase of the plasma membrane, increases. 相似文献
17.
I. V. Shemarova S. M. Korotkov V. P. Nesterov 《Journal of Evolutionary Biochemistry and Physiology》2011,47(4):360-365
The inotropic Cd2+ action on frog heart is studied with taking into account its toxic effects upon mitochondria. Cd2+ at concentrations of 1, 10, and 20 mM is established to decrease dose dependently (21.3, 50.3, and 72.0%, respectively) the
muscle contraction amplitude; this is explained by its competitive action on the potential-controlled Na2+-channels of the L-type (Cav 1.2). In parallel experiments on isolated rat heart mitochondria (RHM) it was shown that Cd2+ at concentrations of 15 and 25 mM produces swelling of non-energized and energized mitochondria in isotonic (with KNO2 and NH2NO3) and hypoosmotic (with 25 mM CH3COOK) media. Study of oxidative processes in RHM by polarographic method has shown 20 mM Cd2+ to disturb activity of respiratory mitochondrial chain. The rate of endogenous respiration of isolated mitochondria in the
medium with Cd2+ in the presence of malate and succinate was approximately 5 times lower than in control. In experimental preparations, addition
into the medium of DNP—uncoupler of oxidation and phosphorylation did not cause an increase of the oxygen consumption rate.
Thus, the obtained data indicate that a decrease in the cardiac muscle contractility caused by Cd2+ is due not only to its direct blocking action on Ca2+-channels, but also is mediated by toxic effect on rat heart mitochondria, which was manifested as an increase in ion permeability
of the inner mitochondrial membrane (IMM), acceleration of the energy-dependent K+ transport into the matrix of mitochondria, and inhibition of their respiratory chain. 相似文献
18.
Dinesh K. Yadav Sri Ramya Tata John Hunt Erik C. Cook Trevor P. Creamer Nicholas C. Fitzkee 《Biomolecular NMR assignments》2017,11(2):215-219
Calcineurin (CaN) plays an important role in T-cell activation, cardiac system development and nervous system function. Previous studies have demonstrated that the regulatory domain (RD) of CaN binds calmodulin (CaM) towards the N-terminal end. Calcium-loaded CaM activates the serine/threonine phosphatase activity of CaN by binding to the RD, although the mechanistic details of this interaction remain unclear. It is thought that CaM binding at the RD displaces the auto-inhibitory domain (AID) from the active site of CaN, activating phosphatase activity. In the absence of calcium-loaded CaM, the RD is disordered, and binding of CaM induces folding in the RD. In order to provide mechanistic detail about the CaM–CaN interaction, we have undertaken an NMR study of the RD of CaN. Complete 13C, 15N and 1H assignments of the RD of CaN were obtained using solution NMR spectroscopy. The backbone of RD has been assigned using a combination of 13C-detected CON-IPAP experiments as well as traditional HNCO, HNCA, HNCOCA and HNCACB-based 3D NMR spectroscopy. A 15N-resolved TOCSY experiment has been used to assign Hα and Hβ chemical shifts. 相似文献
19.
Aleksandra Jovanovic Milan Obradovic Emina Sudar Milovanovic Alan J. Stewart Samantha J. Pitt Dragan Alavantic Ema Aleksic Esma R. Isenovic 《Molecular and cellular biochemistry》2017,436(1-2):49-58
The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na+/K+-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150–200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the α1 subunit of Na+/K+-ATPase by 30% (p < 0.05), expression of total α1 subunit of Na+/K+-ATPase by 31% (p < 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p < 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p < 0.01) and 62% (p < 0.05), respectively. Our results suggest that a HF diet alters cardiac Na+/K+-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats. 相似文献
20.
Gusev GP Ivanova TI 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2003,173(5):429-435
The present study was designed to evaluate the role of protein phosphatases in regulation of sodium transport in the marsh frog erythrocytes using 22Na as a tracer. For this purpose the cells were treated with several known inhibitors of protein phosphatases. In standard isotonic medium, exposure of the cells to 10 mmol l(-1) NaF, 20 nmol l(-1) calyculin A or 0.1 mmol l(-1) cantharidin resulted in a significant (1.7-fold) increase in unidirectional ouabain-insensitive Na+ influx. The Na+ influx in frog red cells was progressively activated as the medium osmolality was increased by addition of 100, 200 or 300 mmol l(-1) sucrose to standard isotonic medium. The stimulatory effect of protein phosphatase blockers on Na+ influx was much higher in hypertonic medium containing 100 or 200 mmol l(-1) sucrose than that in isotonic medium. Stimulation of Na+ transport enhanced with increasing concentrations of calyculin A, and half-maximal activation (EC50) was obtained at 16 nmol l(-1). However, Na+ influx induced by strong hypertonic treatment (+300 mmol l(-1) sucrose) was not altered further in the presence of protein phosphatase inhibitors. The changes in Na+ influx evoked by protein phosphatase inhibitors and hypertonic treatment were associated with a rise in the intracellular Na+, but not K+, content. Enhancement in Na+ influx after addition of protein phosphatase blockers to cell suspension in isotonic or hypertonic media was almost completely inhibited by Na+/H+ exchange inhibitors, amiloride and ethyl-isopropyl-amiloride. The basal Na+ influx in frog erythrocytes in isotonic medium was relatively low (1.7 mmol/l cells/h) and not affected by 1 mmol l(-1) amiloride. Thus, the data obtained clearly indicate that Na+/H+ exchanger in the marsh frog red blood cells is under tight regulatory control, in all likelihood via protein phosphatases of types PP-1 and PP-2A. 相似文献