Regulation of ATP-sensitive potassium channels by phosphorylation.
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Biomedical subjects
Publications and source records attributed to P Light.
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The activity of ATP-sensitive potassium channels of skeletal muscle is controlled by changes in the bioenergetic state of the cell. These channels are inactive in unfatigued muscle and become activated during fatigue. It has been postulated that ATP-sensitive potassium channels shorten the action potential duration, increase the potassium efflux and contribute to the decrease in force during fatigue. Although blocking ATP-sensitive potassium channels during fatigue prolongs the action potential duration and decreases the potassium efflux as expected, it does not affect the rate of fatigue development as observed from the decrease in tetanic force. Even though such results are not consistent with the hypothesis that ATP-sensitive potassium channels contribute to the decrease in force during fatigue, a reduced capacity of skeletal muscles to recover their tetanic force following fatigue is also observed when ATP-sensitive potassium channels are blocked during fatigue, suggesting that these channels have a myoprotective effect. It is thus possible that removing this myoprotection during fatigue results in deleterious effects which counteract the expected slower decrease in force. However ATP-sensitive potassium channel openers also fall to affect the rate of fatigue development. Therefore, the results obtained so far do not support the hypothesis that ATP-sensitive potassium channels contribute to the decrease in force during fatigue.
The goal of this study was to determine how blocking ATP-sensitive K+ channels with tolbutamide affects the excitability and contractility of intact frog sartorius muscle during fatigue development. Fatigue was elicited with one tetanic contraction every sec for 3 min. During fatigue the resting potential decreased by 10 mV although the action potential overshoot remained constant. The addition of 2 mmol.liter-1 tolbutamide 60 min before fatigue did not modify the effect of fatigue on the resting potential and action potential overshoot. During fatigue development the half-repolarization time of control muscles increased by 0.26 msec in control muscles, although it increased by 0.77 msec in the presence of 2 mmol.liter-1 tolbutamide; the difference was significant. The decrease in force during fatigue development was not affected by 2 mmol.liter-1 tolbutamide (added 60 min before fatigue), whereas the recovery of force after fatigue was slower in tolbutamide- exposed muscles than in control muscles. Addition of 2 mmol.liter-1 tolbutamide after 5 min of recovery reduced the recovery rate of the resting potential and half-repolarization time, but did not affect the recovery of tetanic force during the first 40 min. Our results are consistent with the hypothesis that ATP-sensitive K+ channels are activated during fatigue development and that they contribute to the repolarization phase of action potentials, but they do not support the hypothesis that ATP-sensitive K+ channels contribute to the decrease in force.
The goal of this study was to characterize the effects of tolbutamide and glyburide, two known KATP channel blockers, on intact, unfatigued sartorius muscle fibres of the frog, Rana pipiens. Tetanic contractions were elicited by field stimulation with 200 ms long train of pulses (0.5 ms, 6 V, 140 Hz). Resting and action potentials were measured using conventional microelectrodes. At pHo 7.2 (extracellular pH), the tetanic force was unaffected by 0.5 mM and 1.0 mM tolbutamide, but at 2.0 mM it decreased by 15.5 +/- 1.0%. The effect of tolbutamide on the tetanic force was significantly greater at pHo 6.4: all three tolbutamide concentrations caused a significant decrease in tetanic force, being 62.3 +/- 9.4% at 2 mM. In the presence of tolbutamide a large number of fibres became unexcitable at pHo 6.4, but not at pHo 7.2. Glyburide at 10 microM, on the other hand, caused a 5-7% decrease in tetanic force at both pHo 6.4 and 7.2, but no further decreases in tetanic force were observed when the glyburide concentration was increased up to 100 microM. Unlike tolbutamide, glyburide did not affect the excitability of muscle fibres, but significantly prolonged the repolarization phase of action potentials, especially at pHo 6.4. We suggest that several of the tolbutamide effects reported in this study cannot be accounted for by a direct effect on KATP channels, and that the large decrease in membrane excitability and muscle contractility in the presence of tolbutamide must seriously be taken into consideration when this channel blocker is used to study the physiological role of KATP channels in intact muscle fibres.
Many turtles exhibit temperature-dependent sex determination. We have examined the hypothesis that incubation temperature causes a differential expression of steroidogenic enzymes in embryonic turtles. The activities of three steroidogenic enzymes were studied histochemically in turtle (Trachemys scripta) embryos at different developmental stages: sexually undifferentiated (Stage 15), differentiating (Stage 17), and differentiated (Stage 26; i.e., hatchling). Steroidogenic enzymes were detected in several tissues prior to, during, and after gonadal differentiation in embryos incubated at both male-producing and female-producing temperatures. In all embryos, ene-5-3 beta-hydroxysteroid dehydrogenase (HSDH) was detected only in adrenal tissue. 3 alpha-HSDH was localized in adrenal tissue, as well as in the mesonephros and liver. 17 beta-HSDH was evident in mesonephric, hepatic, and gut tissues. In hatchlings, ene-5-3 beta-HSDH and 3 alpha-HSDH were evident in the adrenal gland, whereas 3 alpha-HSDH and 17 beta-HSDH were present in the mesonephros and liver. While there was some variation in the activities of these enzymes during development, no temperature-specific pattern was apparent. At no stage were the enzymes observed in genital ridge/gonad. Our results show that T. scripta embryos possess enzymes necessary for steroid hormone synthesis. The segregated distributions of the enzymes suggest that a multi-organ regulatory system may mediate embryonic steroidogenesis. Our results do not indicate the genital ridge/gonad the principle site of steroid synthesis, although it may possess other enzymes that influence steroidogenesis.
The effects of increasing the extracellular K+ concentration on the capacity to generate action potentials and to contract were tested on unfatigued muscle fibers isolated from frog sartorius muscle. The goal of this study was to investigate further the role of K+ in muscle fatigue by testing whether an increased extracellular K+ concentration in unfatigued muscle fibers causes a decrease in force similar to the decrease observed during fatigue. Resting and action potentials were measured with conventional microelectrodes. Twitch and tetanic force was elicited by field stimulation. At pHo (extracellular pH) 7.8 and 3 mmol K+.L-1 (control), the mean resting potential was -86.6 +/- 1.7 mV (mean +/- SEM) and the mean overshoot of the action potential was 5.6 +/- 2.5 mV. An increased K+ concentration from 3 to 8.0 mmol.L-1 depolarized the sarcolemma to -72.2 +/- 1.4 mV, abolished the overshoot as the peak potential during an action potential was -12.0 +/- 3.9 mV, potentiated the twitch force by 48.0 +/- 5.7%, but did not affect the tetanic force (maximum force) and the ability to maintain a constant force during the plateau phase of a tetanus. An increase to 10 mmol K+.L-1 depolarized the sarcolemma to -70.1 +/- 1.7 mV and caused large decreases in twitch (31.6 +/- 26.1%) and tetanic (74.6 +/- 12.1%) force. Between 3 and 9 mmol K+.L-1, the effects of K+ at pHo 7.2 (a pHo mimicking the change in interstitial pH during fatigue) and 6.4 (a pHo known to inhibit force recovery following fatigue) on resting and action potentials as well as on the twitch and tetanic force were similar to those at pHo 7.8. Above 9 mmol K+.L-1 significant differences were found in the effect of K+ between pHo 7.8 and 7.2 or 6.4. In general, the decrease in peak action potential and twitch and tetanic force occurred at higher K+ concentrations as the pHo was more acidic. The results obtained in this study do not support the hypothesis that an accumulation of K+ at the surface of the sarcolemma is sufficiently large to suppress force development during fatigue. The possibility that the K+ concentration in the T tubules reaches the critical K+ concentration necessary to cause a failure of the excitation-contraction coupling mechanism is discussed.
We conducted two experiments to assess the role of referential speech during sign training in which the spoken words corresponding to signs were receptively known to the participants. An alternating treatments design was used to compare sign acquisition across two teaching conditions in which referents were presented either with or without the corresponding verbal label. During the first experiment, signs were taught concurrently; during the second experiment, signs within each of the respective conditions were taught in a serial fashion. In both experiments, signs taught by total communication were acquired faster than those taught by sign-alone training.
Female squirrels were injected at birth with 50 or 1000 micrograms testosterone propionate (TP); control males and females were treated with oil vehicle. Squirrels were gonadectomized at 47 days of age. Body mass was recorded weekly and plasma luteinizing hormone (LH) was determined once monthly over the next year. Marked annual cycles in body mass were manifested by 30 out of 31 squirrels. Peak body mass and peak-to-trough differences were greater for control male and TP-female squirrels than for control female squirrels. Trough body weights did not differ among the groups. Luteinizing hormone was detectable in all male and most androgenized females but not in any control female squirrels during the first 4 mo after gonadectomy. Peak LH values were significantly greater for control male than for control female squirrels and were not influenced by neonatal androgenization in females. Testosterone propionate treatment also did not affect sex differences in timing of LH peaks or the total number of months in which LH was detectable. We conclude that testicular hormones secreted during the early postnatal period induce sex differences in the circannual pattern of weight change and some aspects of LH secretion. Complete masculinization, however, either requires more extensive action of gonadal hormones, perhaps both pre- and postnatally, or occurs through some androgen-independent mechanism.
We examined the effects of receptive speech on the acquisition of manual signing among three mentally retarded children. In an alternating treatments design, we compared the acquisition of expressive signs that were, versus were not, in a child's receptive vocabulary. The children were trained via total communication in which pictorial referents were named during sign training. Signs corresponding to known words were generally acquired faster and retained better than signs corresponding to unknown words. We conducted posttests to assess the stimulus control of signing and any changes in expressive and receptive signing and speech. Observed changes in performance could be accounted for by attention to aspects of the stimulus complex during training and functional equivalence of stimuli established by training.
Attempts to represent the occlusion of a farther object by a nearer one are infrequent in young children's drawings. Instead they typically draw the objects side by side or one above the other. This does not appear to reflect a limitation of skill, but rather a concern with the array of objects per se as opposed to the child's own particular view. Two experiments are reported which attempt to assess children's ability to produce view-specific drawings by creating a context that clearly demands such drawings. In a "communication game," drawings were produced by one child so that another could identify the chair he had been sitting on. In a first experiment, compared to a control condition this game produced significantly more view-specific drawings from 7- and 8-year-olds, but not from 5- and 6-year-olds. A second experiment with 5- and 6-year-olds was also ineffective in promoting view-specific drawings at this age.
Children who fail spatial perspective-taking tasks of the "3 mountains" variety apparently preferentially select pictures showing their own view. It has been suggested that this might arise, at least in part, because children in such tasks have been given particularly good views of the arrays. To test this, an experiment was conducted with 40 4-6-year-olds in which children were tested from both "good" and "poor" viewing positions. As hypothesized, children did not show any bias toward their own view when it was a poor one. However, when they themselves had a good view of the objects, they chose their own rather than another equally good view. Thus, 2 selection principles appear to operate hierarchically, selection of good view having priority over selection of own view.
Highly purified bullfrog growth hormone (GH) was tested for growth promoting activity in rats and bullfrogs (Rana catesbeiana). In repeated assays, the potency of bullfrog GH in the rat tibia assay was 1 X bovine GH, which is significantly greater than all other non-mammalian GHs tested. It also stimulated significant whole body growth in immature hypophysectomized rats injected daily for 16 days. In bullfrogs, the bullfrog GH (about 2 microgram/injection) stimulated growth and appetite in intact frogs, and improved survival in hypophysectomized frogs. In contrast, even relatively high doses of bovine GH (up to 200 microgram/injection) were inactive in the bullfrog.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.