Voltage-gated potassium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The 6TM family of K channels comprises the voltage-gated KV subfamilies, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 7TM, termed BK) and the Ca2+-activated SK subfamily. These channels possess a pore-forming α subunit that comprise tetramers of identical subunits (homomeric) or of different subunits (heteromeric). Heteromeric channels can only be formed within subfamilies (e.g. Kv1.1 with Kv1.2; Kv7.2 with Kv7.3). The pharmacology largely reflects the subunit composition of the functional channel

Voltage-gated potassium channels (Kv) in GtoPdb v.2021.3

The 6TM family of K channels comprises the voltage-gated KV subfamilies, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 7TM, termed BK) and the Ca2+-activated SK subfamily. These channels possess a pore-forming α subunit that comprise tetramers of identical subunits (homomeric) or of different subunits (heteromeric). Heteromeric channels can only be formed within subfamilies (e.g. Kv1.1 with Kv1.2; Kv7.2 with Kv7.3). The pharmacology largely reflects the subunit composition of the functional channel

Immunomodulation of voltage-dependent K+ channels in macrophages: molecular and biophysical consequences

Voltage-dependent potassium (Kv) channels play a pivotal role in the modulation of macrophage physiology. Macrophages are professional antigen-presenting cells and produce inflammatory and immunoactive substances that modulate the immune response. Blockage of Kv channels by specific antagonists decreases macrophage cytokine production and inhibits proliferation. Numerous pharmacological agents exert their effects on specific target cells by modifying the activity of their plasma membrane ion channels. Investigation of the mechanisms involved in the regulation of potassium ion conduction is, therefore, essential to the understanding of potassium channel functions in the immune response to infection and inflammation. Here, we demonstrate that the biophysical properties of voltage-dependent K+ currents are modified upon activation or immunosuppression in macrophages. This regulation is in accordance with changes in the molecular characteristics of the heterotetrameric Kv1.3/Kv1.5 channels, which generate the main Kv in macrophages. An increase in K+ current amplitude in lipopolysaccharide-activated macrophages is characterized by a faster C-type inactivation, a greater percentage of cumulative inactivation, and a more effective margatoxin (MgTx) inhibition than control cells. These biophysical parameters are related to an increase in Kv1.3 subunits in the Kv1.3/Kv1.5 hybrid channel. In contrast, dexamethasone decreased the C-type inactivation, the cumulative inactivation, and the sensitivity to MgTx concomitantly with a decrease in Kv1.3 expression. Neither of these treatments apparently altered the expression of Kv1.5. Our results demonstrate that the immunomodulation of macrophages triggers molecular and biophysical consequences in Kv1.3/Kv1.5 hybrid channels by altering the subunit stoichiometry

Potassium Channel and NKCC Cotransporter Involvement in Ocular Refractive Control Mechanisms

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia

Optical control of L-Type Ca2+ channels using a diltiazem photoswitch

L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control

MEASUREMENTS OF THE QUADRUPOLE MOMENT OF THE FIRST EXCITED STATE OF THE NUCLEI GERMANIUM-74,76, AND PALLADIUM-108 BY HEAVY ION COULOMB EXCITATION

Abstract not availabl

Focando em melhorias de desempenho a curto prazo não produz melhorias a longo prazo

The short-term emphasis engendered by No Child Left Behind (NCLB) has focused research predominantly on unraveling the complexities and uncertainties in assessing short-term results, rather than developing methods and assessing results over the longer term. In this paper we focus on estimating long-term gains and address questions important to evaluating schools and identifying educational policies and practices that produce long-term sustained gains. Estimates are made of annual pass rates on state exams using fixed effect models for six years of pass rates at grades 3, 6, 8 and 10; the percentages of schools making statistically significant gains, gains, losses, and statistically significant losses in pass rates are determined. Estimates are contrasted using models that include and exclude demographic characteristics. The percentages of schools with statistically significant gains varied markedly from 38 to 6 at grades 6 and 10, respectively; the percentage of schools with statistically significant declines ranged from less than 8 percent at grades 3, 6, and 8, to 23 percent at grade 10. Including demographics increased the percentages of schools with statistically significant gains and lowered the percentages with statistically significant declines. The results suggest that schools with higher proportions of free-reduced lunch and minority students are more likely to have statistically significant gains with demographic controls. Estimates of pass rate trends are made using Monte Carlo simulations; from these simulations the percentages of schools that may be mislabeled as having statistically significant gains and losses are determined. Even with six years of trend data, results suggest that chance can still play a significant role in mislabeling school performance, especially in grades having weak overall trends.El énfasis de corto plazo generada por la ley NCLB ha centrado principalmente la investigación en desentrañar las complejidades e incertidumbres en la evaluación de resultados a corto plazo, en lugar de desarrollar métodos y evaluación de los resultados a más largo plazo. En este artículo nos centramos en la estimación de ganancias a largo plazo y tratamos cuestiones importantes para la evaluación de las escuelas y la identificación de las políticas y prácticas educativas que producen mejoras sostenidas a largo plazo. Se realizan estimaciones de los índices de aprobación en exámenes estatales anuales utilizando modelos de efectos fijos para los seis años en los grados 3 , 6, 8 y 10 con índices de aprobación.  Se determinaron los índices de aprobación de los porcentajes de escuelas con mejoras estadísticamente significativas, mejoras, empeoramiento y empeoramiento estadísticamente significativo. Las estimaciones se contrastaron utilizando modelos que incluyen y no incluyen características demográficas. Los porcentajes de las escuelas con las mejoras estadísticamente significativas variaron notablemente 38-6 en los grados 6 y 10 respectivamente , y el porcentaje de escuelas con empeoramientos estadísticamente significativos varió de menos del 8 por ciento en los grados 3, 6 y 8 , hasta 23 por ciento en el grado 10. Incluyendo datos demográficos se aumentó los porcentajes de las escuelas con mejoras estadísticamente significativas y se disminuyó los porcentajes con empeoramiento estadísticamente significativos. Los resultados sugieren que las escuelas con mayores proporciones de estudiantes que reciben subsidios de almuerzo y con estudiantes de minorías son más propensos a tener ganancias estadísticamente significativas con los controles demográficos. Las estimaciones de la evolución del tipo de paso se realizan utilizando simulaciones de Monte Carlo, a partir de estas simulaciones se determinan los porcentajes de las escuelas que pueden ser mal identificadas como teniendo ganancias y pérdidas significativa . Incluso con seis años de datos sobre tendencias, los resultados sugieren que el azar todavía puede jugar un papel significativo en la medición del rendimiento escolar, especialmente en los grados que tienen tendencias generales de mayor debilidadO foco no curto prazo gerado pela NCLB fez que a pesquisa seja focada principalmente para desvendar as complexidades e incertezas na avaliação de resultados de curto prazo, em vez de desenvolver métodos e avaliação de resultados no longo prazo. Neste artigo vamos nos concentrar na estimativa de ganhos a longo prazo e tratar questões importantes para a avaliação das escolas e a identificação de políticas e práticas educacionais que produzem melhorias sustentaveis a longo prazo. Estimativas dos índices de aprovação foram realizadas em testes anuais estaduais, utilizando modelos de efeitos fixos para os seis anos nas classes 3, 6, 8, e 10  com índices de aprovação. Foram determinadas os índices de aprovação do percentual de escolas com melhorias estatisticamente significativas, melhorias, retrocessos, e retrocessos estatisticamente significativos. As estimativas foram comparadas com modelos que incluem e excluem características demográficas. Os percentuais de escolas com melhorias estatisticamente significativas variaram acentuadamente de 38 a 6 nas classes 6 e 10, respectivamente, bem como a percentagem de escolas com retrocessos significativos variou de menos de 8 por cento em notas 3, 6 e 8-23 por cento no grau 10. Incluindo dados demográficos os percentuais de escolas com melhorias estatisticamente significativas foram aumentados e percentagens retrocessos estatisticamente significativos diminuíram. Os resultados sugerem que as escolas com maior proporção de estudantes que recebem subsídios de almoço e estudantes de minorias são mais propensos a ter ganhos estatisticamente significativos com controles demográficos. As estimativas da evolução da etapa são realizadas por meio de simulações de Monte Carlo, e com base nessas simulações o percentual de escolas que podem ser erroneamente identificado como tendo ganhos e perdas significativas foram determinados. Mesmo com seis anos de tendência de dados, os resultados sugerem que a sorte ainda pode desempenhar um papel significativo na medição de desempenho escolar, especialmente nas series que tem tendências gerais a serem mais fracas

What a difference a day makes: Estimating daily learning gains during kindergarten and first grade using a natural experiment

Knowing whether time spent in formal schooling increases student achievement, and by how much, is important for policymakers interested in determining efficient use of resources. Using the ECLS-K, we exploit quasi-randomness in the timing of assessment dates to examine this question. Conservative estimates suggest a year of school results in gains of about one standard deviation above normal developmental gains in both reading and math test scores. The results are statistically significant and extremely robust to specification choice, supporting quasi-randomness of test dates. Estimates of skill accumulation due to formal schooling do not vary based on socioeconomic characteristics.School resources Natural experiment School year length