Interactions of insecticides with erythrocyte membranes     

M.C. Antunes-Madeira  A.P. Carvalho  Vitor M.C. Madeira 《Pesticide biochemistry and physiology》1981,15(1):79-89

Insecticides exert antilytic effects on pig erythrocytes by preventing osmotic disruption of membranes in critical hypotonic saline media. The order of effectiveness is the following: lindane > aldrin ≈ azinphos > parathion ≈ DDT > malathion; empirical protective indexes estimated for K⁺ leakage, at 0.09 M NaCl, were 5.6, 3.9, 2.9, 2.8, and 2.0, respectively. Erythrocytes swell and hemolyze in solutions containing glycerol below 0.6 M. At higher concentrations and temperatures below 20°C, the extent of cell lysis is very limited and virtually nil in 1 M glycerol. In hypertonic glycerol solutions, cells swell until the initial equilibrium volume is reached and, then, the swelling process ceases. Swelling in 1 M glycerol is related to its permeation through hydrophobic membrane domains. The activation energies of permeation are similar to the dehydration energies of glycerol molecules. As the temperature is increased above 20°C, erythrocytes undergo lysis. The organophosphorus insecticides, parathion and azinphos (10^?4M), significantly increase the swelling rates and the extent of cell lysis. Malathion and chlorinated insecticides do not exert apparent effects. However, these compounds are effective in liposomes reconstituted with lipids extracted from erythrocyte membranes.  相似文献   

Isomerization and Beckmann rearrangement reactions in the metabolism of methomyl in rats     

Kurt Huhtanen  H.Wyman Dorough 《Pesticide biochemistry and physiology》1976,6(6):571-583

Methomyl {S-methyl-N-[(methylcarbamoyl)oxy]thioacetimidate}, also known as Lannate, may exist in two geometric configurations but the more stable syn isomer is the form applied as an insecticide. In the rat, syn[¹⁴CN]methomyl [CH₃S(CH₃)CNOC(O)NHCH₃] was metabolized to respiratory ¹⁴CO₂ and $\text{CH}{}_3{}^{14}\text{CN}$ in a ratio of about 2 to 1. Studies with the anti isomer showed that it was metabolized predominately to $\text{CH}{}_3{}^{14}\text{CN}$. These and other data are presented supporting the contention that syn methomyl is partially isomerized to the anti isomer in the animal prior to the hydrolysis of the ester linkage. After hydrolysis, the syn oxime [CH₃S(CH₃)¹⁴CNOH] is further metabolized to ¹⁴CO₂ while the anti oxime is metabolized to $\text{CH}{}_3{}^{14}\text{CN}$. Proposed immediate precursors to the carbon dioxide and acetonitrile, formed by Beckmann rearrangement of the syn and anti oximes, are CH₃S¹⁴C(O)NHCH₃ and $\text{[}\text{CH}{}_3{}^{\mathrm{14\oplus }}\text{CNSCH}{}_3\text{]x}{}^{\mathrm{?}}$, respectively.  相似文献   

Selective alterations of membrane properties of cultured human liver cells caused by the insecticide DDT     

K. Buff  A. Bründl 《Pesticide biochemistry and physiology》1984,22(1):36-42

A variety of membrane-specific parameters was examined in both intact cells and isolated plasma membranes following exposure of cultured human liver cells to the insecticide 1,1-(2,2,2-trichloroethylidene)bis(4-chloro)benzene (DDT). Uptake of DDT was at equilibrium within 6 hr. In contrast, a decrease in the number of β-adrenergic hormone receptors first became significant after 48 hr of cell exposure. Whereas the uptake was largely reversible, the loss in the number of β receptors did not recover after DDT-exposed cells were cultured in fresh medium lacking the insecticide. Experiments in vitro substantiated the time lag of the biological effect. The decrease in receptor proteins was persistent in membranes with increased phospholipid unsaturation. Temperature-activity profiles (“Arrhenius plots”) of $\text{Na}{}^{\mathrm{+}}\text{K}{}^{\mathrm{+}}\text{-ATPase}$ and 5′-nucleotidase were unchanged. Endogenous tryptophan fluorescence of membrane proteins was lower in membranes from DDT-exposed cells. These selective alterations in membrane parameters suggest a specific interaction of DDT with membrane proteins; interference with cellular protein synthesis is possible. The results indicate that membrane lipid “fluidization” does not play a physiologically important role in the mechanism of DDT action in biomembranes.  相似文献   

The metabolism of p,p′-DDT by the feral pigeon (Columba livia)     

M.S. Sidra  C.H. Walker 《Pesticide biochemistry and physiology》1980,14(1):62-71

Male feral pigeons were dosed with ring-labeled $\text{[}{}^{14}\text{C}\text{]p,p′-}\text{DDT}$ and the tissues and droppings analyzed for total ¹⁴C, extractable ¹⁴C, and metabolites. Only 16% of an intraperitoneal dose of 1.5–2.2 mg kg^?1 was voided in the droppings over 28 days; the rate of loss reached a maximum on the 14th day and then fell quickly away. The rate of removal of ¹⁴C in droppings was low in comparison to that found in the rat and the Japanese quail. When pigeons were dosed with 32–38 mg kg^?1 DDT per bird, and killed after 77 days, 5.4% of the dose was eliminated in droppings and 87% was recovered in the body. The tissues and droppings from this experiment were analyzed for DDT and its metabolites. Of the ¹⁴C remaining in tissues 88% was accounted for as the apolar compounds DDE, DDT, and DDD. Approximately half of the ¹⁴C in droppings was present as DDE, DDT, and DDD, whereas 27–35% was apparently in conjugated form, extractable from aqueous solutions by ethyl acetate after prolonged acid hydrolysis. Two polar metabolites were isolated from the acid-released material. One was p,p′-DDA; the other was extractable from aqueous solution at pH 8 and was tentatively identified as a monohydroxy derivative of p,p′-DDT. DDE accounted for 93% of the ¹⁴C present as metabolites in tissues and droppings, clearly indicating the importance of this intermediate in this study. The metabolism of DDT in the feral pigeon is discussed in relation to its metabolism by other species.  相似文献   

Deuterium isotope effects on the formation of mercapturic acids from lindane in rats     

Norio Kurihara  Tetsuya Suzuki  Minoru Nakajima 《Pesticide biochemistry and physiology》1980,14(1):41-49

Metabolism experiments with rats showed that significant isotope effects ($\text{k}{}_{\mathrm{<mtext>H</mtext>}}\text{k}{}_{\mathrm{<mtext>D</mtext>}}\text{= 2.4}\text{to}\text{3.5}$) were associated with the in vivo formation of dichloro and trichlorophenylmercapturic acids from a 1:1 mixture of normal and hexadeuterated lindane. This is evidence that rate-determining dehydrogenation and dehydrochlorination, both of which proceed with significant isotope effects, are essential in the pathway of dichloro- and trichlorophenylmercapturic acid formation from lindane. No significant primary isotope effects were associated ($\text{k}{}_{\mathrm{<mtext>H</mtext>}}\text{k}{}_{\mathrm{<mtext>D</mtext>}}\text{= 1.31 ± 0.17}$) with the formation of monochlorophenylmercapturic acid. This suggests that the 1,2-dechlorination to tetrachlorocyclohexene followed by glutathione conjugation is the probable pathway that produces this metabolite from lindane.  相似文献   

Comparative metabolism of six ethoxychlor analogs and DDT in DDT-resistant and susceptible strains of the house fly Musca domestica L     

Mohammed Y.H. Farroqui  Robert L. Metcalf 《Pesticide biochemistry and physiology》1983,19(2):210-220

The metabolic fate of six ³H-ring-substituted ethoxychlor analogs with altered aliphatic moieties and [¹⁴C]p,p′-DDT was investigated in susceptible and DDT-resistant strains of the house fly Musca domestica Linnaeus. The chloroalkane analogs, dichloroethane, chloropropane, and dichloropropane were primarily metabolized to the corresponding dehydrochlorinated products. This pathway was relatively more prominent in the resistant strain than in the susceptible strain. Biotransformation and detoxication of the isobutane, nitropropane, and neopentane derivatives was through microsomal oxidation (O-deethylation) of aryl ethoxy degradophores, and oxidation of the aliphatic moieties to produce the corresponding benzophenones, with no substantial differences between the resistant and susceptible strain. There was a strong correlation between the Taft ($\text{σ}{}^1$) values for the altered aliphatic moieties of chloroalkane analogs and their rate of dehydrochlorination in both the strains. These results suggest the importance of altered aliphatic moieties in developing resistance-proof DDT derivatives.  相似文献   

Cytochrome P-450 content and aldrin epoxidation to dieldrin in isolated rat hepatocytes     

Norio Kurihara  Nobuaki Hori  Reiji Ichinose 《Pesticide biochemistry and physiology》1984,21(1):63-73

A rat hepatocyte suspension effectively epoxidized aldrin to dieldrin with a V_max of 7.19 mol/mol P-450/min and a K_m of 9.27 μM. Viability and metabolic activity were stable for 6 hr after isolation when cells were maintained at room temperature (20°C) with the gentle introduction of $\text{O}{}_2\text{CO}{}_2$ onto the surface of the suspension. The cytochrome P-450 content of the suspension was 303 pmol/10⁶ cells. Primary maintenance culture of the cells also epoxidized aldrin. During culture for 3 days, metabolic activity decreased slowly day by day. Metabolic activity of microsomal fraction from rat liver was also examined. Microsomes epoxidized aldrin with a V_max of 5.11 mol/mol P-450/min and a K_m of 1.64 μM. Significant loss of some subspecies of cytochrome P-450 during fractionation of liver homogenate was indicated.  相似文献   

Membrane partitioning of organophosphorus and organochlorine insecticides and its implications for mechanisms of toxicity     

Maria Do Carmo Antunes-Madeira  Vitor M. C. Madeira 《Pest management science》1989,26(2):167-179

Partition coefficients of organophosphorus and organochlorine insecticides were determined in several types of membrane. Insecticide partitioning varied among the membranes under study, depending on temperature, cholesterol content and on the physico-chemical profiles of membrane components and the insecticides themselves. The maximal partitions for DDT, lindane, parathion and malathion in egg phosphatidylcholine bilayers over the temperature range from 10 to 37°C (at which the lipid is in the liquid-crystalline state) were about 260000, 2000, 1000 and 120, respectively. Incorporation of 50 mol% cholesterol in egg phosphatidylcholine bilayers dramatically decreased the partition and almost abolished the temperature effect. First-order phase transitions of dimyristoyl-, dipalmitoyl- and distearoylphosphatidylcholines (DMPC, DPPC and DSPC) were accompanied by a sharp increase in insecticide partition. Furthermore, the insecticides under study were more easily accommodated in bilayers of short-aliphatic-chain lipids, since higher values of partition were obtained in DMPC bilayers. Partition values in native membranes depended considerably on the membrane type and composition and were higher in sarcoplasmic reticulum (SR) and mitochondria than in brain microsomes, myelin and erythrocytes. Identical results were obtained in related liposomes of total extracted lipids, although the absolute partitions showed decreased values. In general, the incorporation of insecticides correlated reasonably with the cholesterol content of the membranes. The order of partitioning of the above insecticides did not run parallel with their toxicity to mammals and, both in model and in native membranes, followed the sequence: DDT ? lindane > parathion > malathion.  相似文献   

Picrotoxinin receptor in the central nervous system of the American cockroach: Its role in the action of cyclodiene-type insecticides     

Keiji Tanaka  Jeffrey G. Scott  Fumio Matsumura 《Pesticide biochemistry and physiology》1984,22(1):117-127

The nature of the picrotoxinin receptor was studied using the central nervous system (CNS) of the American cockroach. It first was confirmed by using an electrophysiological technique that the abdominal nerve cord of the American cockroach was sensitive to picrotoxinin. By using a $\text{[}{}^3\text{H]α-dihydropicrotoxinin}$ binding test it was determined that the picrotoxinin receptor in CNS of this insect had a higher affinity toward picrotoxinin and heptachlor epoxide than the corresponding receptor in the rat brain. Also, the cockroach brain preparation had a higher percentage of specific binding in the total binding, making this material suitable for receptor studies. By using a sucrose density centrifugation technique, it was determined that the fraction sedimented at the interphase of 1.0 to 1.2 M sucrose at 100,000g contained the highest level of specific binding site. The receptor showed a sensitivity to all insecticidal cyclodienes tested, namely photodieldrin, oxychlordane, endrin, heptachlor epoxide, γ-chlordane, dieldrin, aldrin, heptachlor, and isodrin (expressed in the order of potency). Among four BHC isomers, the γ-isomer showed the highest potency to bind with this receptor.  相似文献   

Metabolism of lindane in house flies: Metabolic desaturation,dehydrogenation and dehydrochlorination,and conjugation with glutathione     

Keiji Tanaka  Norio Kurihara  Minoru Nakajima 《Pesticide biochemistry and physiology》1976,6(4):392-399

In lindane-treated house flies, a cis-dehydrogenated metabolite, $\text{(}\text{36}\text{45}\text{)-}\text{hexachlorocyclohexene}$, was identified by gas-liquid chromatography and mass spectrometry. The in vitro metabolism study showed that in the presence of NADPH the microsomal fraction of house flies converted lindane to three hexane-soluble metabolites. This conversion was inhibited by piperonyl butoxide, SKF-525A, and carbon monoxide. These metabolites were identified as $\text{(}\text{36}\text{45}\text{)-}\text{hexachlorocyclohexene}$, $\text{(}\text{36}\text{45}\text{)- and (}\text{346}\text{5}\text{)-pentachlorocyclohexene}$ (PCCHE) by gas-liquid chromatography. They, as well as lindane, were excellent substrates for the reaction with the postmicrosomal fraction in the presence of glutathione. While the reaction with lindane-d₆ showed a significant deuterium isotope effect (6.82), that of $\text{(}\text{36}\text{45}\text{)-}\text{PCCHE-d}{}_5$ did not (1.18). Enzymatic conjugation with glutathione probably occurs at the stage of PCCHE.  相似文献   

Induction of glutathione S-transferase by phenobarbital and pesticides in various house fly strains and its effect on toxicity     

T. Hayaoka  W.C. Dauterman 《Pesticide biochemistry and physiology》1982,17(2):113-119

The effect of phenobarbital and certain pesticides on glutathione S-transferase activity was investigated. The maximum amount of enzyme induction occurred 96 hr after phenobarbital treatment. Chlorinated hydrocarbons were more effective inducers than the other pesticides evaluated. Phenobarbital treatment did not alter the apparent K_m value but altered the $\text{V}{}_{\mathrm{<mtext>max</mtext>}}$ value of glutathione S-transferase to 3,4-dichloronitrobenzene. The amount of reduced glutathione was not increased by phenobarbital treatment. Pretreatment of house flies with phenobarbital provides some protection against methyl parathion, methyl paraoxon, azinphosmethyl, and methidathion toxicity.  相似文献   

Steric,electronic, and polar parameters that affect the toxic actions of O-alkyl,O-phenyl phosphonothionate insecticides     

Robert L. Metcalf  Robert A. Metcalf 《Pesticide biochemistry and physiology》1984,22(2):169-177

The toxic action of a series of O-alkyl, O-substituted-phenyl alkyl- and aryl-phosphonates and phosphonothionates have been evaluated by correlating the linear free energy parameters for steric (E_s), electronic (σ), and polar ($\text{σ}{}^1$) effects with topical LD₅₀ to the house fly and oral LD₅₀ to the white mouse. In molecules free from major steric interactions with the reactive P atom, variations in these linear free energy parameters account for >90% of the variations in the LD₅₀ values, and the degree of correlation with LD₅₀ is at least as precise as that with the biomolecular rate constants for inhibition of the target-site enzyme acetylcholinesterase. The value of correlations of linear free energy parameters with LD₅₀ in understanding quantitative structure-activity relationships is illustrated.  相似文献   

Mechanism of inhibition reaction of acetylcholinesterase by phenyl N-methylcarbamates: Separation of hydrophobic,electronic, hydrogen bonding and proximity effects of aromatic substituents     

Takaaki Nishioka  Toshio Fujita  Katsuzo Kamoshita  Minoru Nakajima 《Pesticide biochemistry and physiology》1977,7(2):107-121

The association equilibrium constant, $\text{1}\text{K}{}_{\mathrm{d}}$, and the carbamylation constant, k₂, of 53 o-, m-, and p-substituted phenyl N-methylcarbamates with bovine erythrocyte acetylcholinesterase were determined. The $\text{1}\text{K}{}_{\mathrm{d}}$ value varied 1000-fold, whereas the k₂ value did not depend upon the nature and position of substituents. The variation in $\text{log}\text{(}\text{1}\text{K}{}_{\mathrm{d}}\text{)}$ was analyzed using free energy related substituent parameters and regression analyses. The effect of substituents at o-, m-, and p-positions was nicely separated into hydrophobic, electronic, hydrogen bonding, and proximity (steric and field electronic for o-substituents) factors. The physicochemical significance of these factors was established by comparison with those for model organic reactivities. The mechanism of the whole reaction process was elucidated in terms of physical organic chemistry.  相似文献   

Inhibition of Penicillium duponti carboxylesterase by the fungicides captan and folpet     

Karl Neidert  Lee Van Epps  William Welch 《Pesticide biochemistry and physiology》1985,23(2):221-227

Captan, folpet, and perchloromethylmercaptan were effective inhibitors of Penicillium duponti p-nitrophenylpropionate esterase activity (I₅₀ = 0.5 – 2 μM) whereas α-naphthyl acetate esterase activity was not affected by the presence of these compounds. Captan and folpet are both equally effective at pH 7.3 and 8.3. The ionic composition of the medium had strong effects on the degree of inhibition produced by all inhibitors but did not alter esterase activity. Neither succinamide nor phthalimide caused inhibition of the p-nitrophenylpropionate esterase activity: The trichloromethylmercaptan portion of these fungicides appears to be responsible for the observed inhibition. The rapidity of captan and folpet inhibition of esterase activity (complete in < 1 min) compared to the rates of spontaneous decomposition ($\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}\text{> 1}\text{min}$) and the insensitivity of captan and folpet inhibition to hydrogen ion concentration suggest that generation of spontaneous decomposition products is not required for inhibition. The results are consistent with a mechanism in which the entire fungicide molecule binds to the protein followed by enzyme-promoted reactions of captan and folpet which result in loss of esterase activity.  相似文献   

DDT inhibition of Ca-ATPase of the peripheral nerves of the American lobster     

S.M. Ghiasuddin  Fumio Matsumura 《Pesticide biochemistry and physiology》1979,10(2):151-161

A Ca-ATPase highly sensitive to DDT has been found in peripheral nerves of lobster, Homarus americanus. The observed I₅₀ for this Ca-ATPase toward DDT is on the order of 10^?9M and has a low temperature quotien. The ATPase seems to work over a wide range of ATP concentrations. It is stimulated by Ca²⁺ (optimum 0.1 mM) and shows sensitivity to Na⁺ (optimum 20 mM) and K⁺ (optimum 20 mM) ions. The fact that it is highly sensitive to ruthenium red (I₅₀ = 10 μM) suggests that the enzyme is a Ca-ATPase and not a Mg-ATPase. Furthermore the enzyme is not a CaMg-ATPase, since the presence of Mg²⁺ along with Ca²⁺ ion is not required for its activity. DDT is found to inhibit the process of Ca²⁺ binding in the axonic membrane only in the presence of ATP. The evidence suggests the important role of the Ca-ATPase in regulating Ca²⁺ concentrations in the membrane. The possible significance of DDT inhibition of the ATPase is discussed.  相似文献   

Paraoxon formation and hydrolysis by mammalian liver     

L.W. Whitehouse  D.J. Ecobichon 《Pesticide biochemistry and physiology》1975,5(4):314-322

In vitro studies of the desulfuration of parathion at 37°C by hepatic tissue from males and females of nine mammalian species revealed sex and species variation in initial rates of parathion desulfuration and arylesterase-catalyzed hydrolysis of the oxygen analogue, paraoxon. Double reciprocal plots of initial rates of parathion activation for representative males and females of each species gave K_m values ranging from 0.2 × 10^?4?1.0 × 10^?4M parathion. Guinea pigs and rats were the only animals showing sex differences in activation, males possessing higher desulfurating abilities than the corresponding females. Based upon the sex possessing the higher desulfurating ability, the species pattern of decreasing activity was hamster > guinea pig > mouse > rat > rabbit > bovine > dog > porcine > cat. Studies of paraoxon hydrolysis indicated that only rats showed sex differences in hydrolysis, males possessing higher arylesterase activity than females. The species pattern of decreasing hydrolytic activity was in the order mouse > bovine > rat > guinea pig > rabbit > hamster > cat > dog > porcine.  相似文献   

Interactions of insecticides with biological membranes     

Anthony G. Lee  J. Malcolm East  Paul Balgavy 《Pest management science》1991,32(3):317-327

Many insecticides (e.g. DDT, lindane, pyrethroids) are hydrophobic molecules which bind extensively to biological membranes. Binding of insecticides to phospholipid bilayers frequently shows saturation, with binding increasing with increasing insecticide concentration up to some limit, beyond which no further insecticide is incorporated into the bilayer. For lindane, this limit has been shown to correspond to the concentration at which the aqueous phase becomes saturated. Simple alkanes show similar saturation phenomena, and binding of halogenated alkanes can be followed by fluorescence quenching methods. It is shown that effects of hydrophobic molecules on bilayer fluidity are small. Effects of alkanes and insecticides on the activity of the (Ca²⁺-Mg²⁺)-ATPase purified from sarcoplasmic reticulum follow from direct binding to the ATPase, at sites which are not at the lipid-protein interface of the ATPase.  相似文献   

Effect of insecticides on the short-circuit current and resistance of isolated frog skin     

G.D. Webb  R.W. Sharp  J.D. Feldman 《Pesticide biochemistry and physiology》1979,10(1):23-30

The effects of aldrin, carbaryl, α- and γ-chlordane, dichlorodiphenyldichloroethane (DDD), dichlorodiphenyltrichloroethane (DDT), dieldrin, endrin, heptachlor, lindane, methoxychlor, and nonachlor on the short-circuit current and resistance of the isolated intact frog skin were studied. The short-circuit current is approximately equivalent to the rate of active transport of sodium, while the resistance indicates the summed ionic permeability of the skin. At a concentration of 2 × 10^?4M, only carbaryl, DDD, dieldrin, and lindane produced significant (P<0.05, paired t test) changes in the short-circuit current. Nonachlor produced a decrease (P=0.12) in the short-circuit current and also increased the resistance (P=0.07). DDD, dieldrin, and carbaryl caused significant increases in short-circuit current while at the same time the resistance was significantly decreased. Lindane increased both the short-circuit current and the resistance. It was concluded that the frog skin probably contains effective permeability barriers that prevent externally applied insecticides from reaching the site of active sodium transport. It appeared likely that most of the insecticides produced the observed effects on the frog skin by altering the sodium permeability of the outer barrier.  相似文献   

The effect of the mode of application on the toxicity of Androctonus australis hector insect toxin     

Serge De Dianous  Pierre R. Carle  Herv Rochat 《Pest management science》1988,23(1):35-40

The toxicity of the insect toxin from the venom of the scorpion Androctonus australis Hector (AaH IT) was assayed using several ethods of application on various insect species. Activity was only demonstrated by opical application on Musca domestica. Three different solvents were assayed: ethanol + water (50 + 50 by volume), acetone + water (80 + 20 by volume) and acetone + dimethyl sulphoxide (50 + 50 by volume). When using the last two mixtures, LD₅₀ was found to be 1 μg 100 mg^?1 fly. When this activity is compared to that of five synthetic insecticides tested in the same conditions, AaH IT is about 1-5 times more active than propoxur and DDT, 10 times more active than malathion but 200 times less active than deltamethrin. No activity was observed against Aphis craccivora at 15 mg m^?2 in surface-contact tests on glass, or against Culex pipiens pipiens larvae at 2 × 10⁵ ng litre^?1 in water.  相似文献   

Alterations of offspring heart muscle electrical activity transferred by rat male genitors chronically treated with lindane (γ-hexachlorocyclohexane) trace concentrations     

Martin-Pierre Sauviat  Gaston Godeau 《Pesticide biochemistry and physiology》2007,87(2):131-137

Using intracellular microelectrodes, we studied transmembrane resting and action potentials (AP) of left ventricle papillary muscles isolated from the heart of adult lindane-treated (TMG) and untreated (UMG) male genitor rat offspring, obtained by mating untreated female with males chronically treated and untreated with lindane (2 ppb) trace concentrations through beverage. The AP magnitude and duration (APD) were similar in both groups and their response to low temperature (22 °C) unchanged. Lowering the external Ca²⁺ concentration from 2.5 to 0.625 mM prolonged APD in the TMG group but not in the UMG group. In the TMG group, (i) cumulative addition of Sr²⁺ (1 mM) to the physiological solution prolonged APD; (ii) apamin (4 μM) and charybdotoxin (4 μM) prolonged the APD. In conclusion, our data revealed that an altered sensitivity of the Ca²⁺-induced Ca²⁺ inactivation of L-type Ca²⁺ channels and of Ca²⁺-activated K⁺ channels to Ca²⁺ has been transferred to TMG offspring.  相似文献