Extract of Glycyrrhiza glabra root attenuates nociception in experimental pain models: the role of BKCa channels / Extracto de raíz de Glycyrrhiza glabra atenúa la nocicepción en modelos experimentales de dolor: el rol de los canales BKCa

Abstract: The aim of this study was to evaluate the functional interaction of Glycyrrhiza glabra root extract (GGRE) on the large conductance Ca 2+ - activated K + (BKCa) channels expressed in the peripheral nervo us system by using nociception and inflammation models in rodents in vivo . Besides toxicity studies and open field tests, nociception and inflammation tests were performed on rodents. Different doses of GGRE were given orally to rats and mice. Naloxone, in domethacin, morphine, NS1619 and iberiotoxin (IbTX) were administered. GGRE had both anti - nociceptive and anti - inflammatory activity in rats and mice. GGRE exhibited an analgesic effect by decreasing the time - course of the pain threshold or reaction time i n some nociceptive tests. Furthermore, GGRE reduced level of pro - inflammatory cytokines, including TNF - α and IL - 1ß. As a conclusion, GGRE can alleviate the pain sensation of the afferent nerves and can reduce inflammation and associated pain by activating B KCa channels and reducing the levels of TNF - α, IL1ß

Resumen: El objetivo de este estudio fue evaluar la interacción funcional del extracto de raíz de Glycyrr hiza glabra (GGRE) en los canales de K + (BKCa) activados por Ca 2+ de gran conductancia expresados en el sistema nervioso periférico mediante el uso de modelos de nocicepción e inflamación en roedores in vivo . Además de los estudios de toxicidad y las prueb as de campo abierto, se realizaron pruebas de nocicepción e inflamación en roedores. Se administraron por vía oral diferentes dosis de GGRE a ratas y ratones. Se administraron naloxona, indometacina, morfina, NS1619 e iberiotoxina (IbTX). GGRE tenía activi dad tanto antinociceptiva como antiinflamatoria en ratas y ratones. GGRE mostró un efecto analgésico al disminuir la evolución temporal del umbral del dolor o el tiempo de reacción en algunas pruebas nociceptivas. Además, GGRE redujo el nivel de citocinas proinflamatorias, incluidas TNF - α e IL - 1ß. Como conclusión, GGRE puede aliviar la sensación de dolor de los nervios aferentes y puede reducir la inflamación y el dolor asociado activando los canales BKCa y reduciendo los niveles de TNF - α, IL1ß.

Ca(2+)-activated K(+) channel switching in smooth muscle participates in atherosclerosis development in diabetic rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in aorta morphology and Ca(2+)-activated K(+) (KCa) channel expression in the diabetic rats.</p><p><b>METHODS</b>A diabetic rat model was established by a single intraperitoneal injection of streptozotocin (30 mg/kg) after a modified high fat and glucose diet for 8 weeks. Pathological changes in the aorta were observed with HE staining, elastic fiber staining, Masson's trichrome staining and immunohistochemistry. Both the mRNA and protein levels of KCa channels in the aorta were measured by RT-PCR and Western blotting.</p><p><b>RESULTS</b>Early atherosclerotic changes were observed in the aorta wall of the diabetic rats. The mRNA and protein levels of KCa1.1 channel α- and β-subunits were significantly decreased, while the expression of KCa3.1 channels was obviously enhanced in the middle layer of the aorta in the diabetic rats.</p><p><b>CONCLUSION</b>KCa channel switching in smooth muscles may play a role in the development of atherosclerosis in diabetic rats.</p>

Emodin-induced increase in expression of β1 subunit of BKCa channel mediates relaxation of cerebral basilar artery in spontaneously hypertensive rats / 生理学报

The purposes of this study were to investigate the effect of emodin on expression of BKCa channel β1 subunit in basilar artery smooth muscle cells (BASMCs) and electrophysiological characteristics of vascular smooth muscle cells in spontaneously hypertensive rats (SHR). Tail artery pressure measurement instrument was used to measure the change of SHR systolic blood pressure before and after emodin intervention. Single vascular smooth muscle cell was electrically recorded by whole-cell patch-clamp technique. Immunohistochemistry and Western blotting were used to study the distribution and expression of the BKCa channel β1 subunit. The results showed that emodin decreased blood pressure of SHR from (223 ± 16) mmHg to (127 ± 12) mmHg (P < 0.01). There was no difference of blood pressure between emodin-treated SHR and Wistar rats. Emodin significantly increased outward currents of smooth muscle cells in SHR (P < 0.05), and this effect could be reversed by specific inhibitor of BKCa channel, IbTX. Emodin also up-regulated BKCa channel β1 subunit expression in BASMCs. These results suggest that emodin relaxes cerebral basilar artery by enhancing BKCa current via increasing β1 subunit expression in BASMCs.

Impact of BKCa channel in prostate smooth muscle cells on the membrane potential in rats with chronic abacterial prostatitis / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the impact of the BKCa channel in prostate smooth muscle cells (PSMCs) on the membrane potential in SD rats with chronic abacterial prostatitis (CAP).</p><p><b>METHODS</b>CAP models were established in 20 SD rats by castration and injection of 17 beta-estrogen, and another 20 were taken as normal controls. PSMCs were cultured and purified in vitro, and treated with DiBAC4, followed by quantitative observations on the dynamic changes of the cell membrane potential by laser confocal microscopy.</p><p><b>RESULTS</b>The extracellular calcium ion concentration ([Ca2+]o) was increased and the BKCa channel was activated, which induced the hyperpolarization of the PSMC membrane in both the CAP models and normal control rats. This effect was weakened with Iberiotoxin (IbTX), a specific blocker of the BKCa channel, but the amplitude of the hyperpolarization was obviously lower in the CAP than in the control group. The DiBAC4 fluorescence intensity induced by hyperpolarization was 18.78 +/- 2.92 in the former and 38.85 +/- 7.10 in the latter (P < 0.05), while that induced by IbTX was 1.61 +/- 0.46 and 6.12 +/- 1.32 (P < 0.05), respectively.</p><p><b>CONCLUSION</b>Significant decrease of BKCa-mediated hyperpolarization in the CAP model can reduce its abilities of regulating the membrane potential and suppressing the excessive contraction of PSMCs, which may result in pelvic pain syndrome and lower urinary tract symptoms.</p>

Changes of BKCa during aging and its correlation with blood pressure / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes of large-conductance calcium-activated potassium channels (BKCa, MaxiK) during aging and relations between the changes and blood pressure.</p><p><b>METHODS</b>Male spontaneously hypertensive rats (SHR) aged 9, 15, 21, 27, 33 weeks (the number of each weeks SHR was 4) were selected as hypertension group rats, corresponding gender, weeks and number Wistar-Kyoto rats (WKY) as control group rats. Blood pressure of abdominalis aorta of each weeks SHR and WKY were measured by BL-420F experimental system of biological function. The arteria mesenteric minor (AMM) were isolated in blunt dissection method. The vascular smooth muscle cells (VSMCs) of AMM were isolated with prolease. The potassium current, the current after BKCa were blockaded by Tetraethylammonium (TEA) and the capacitance of membrane (Cm) of VSMCs of AMM were recorded with using whole cell patch clamp, and calculated the BKCa current and the BKCa current density. Probe the correlation of the changes of BKCa current density with MABP during aging.</p><p><b>RESULTS</b>The potassium current density and BKCa current density of VSMCs of AMM of SHR were decreasing during aging, however, the changes of WKY had no statistically significance (P > 0.05). The BKCa current density was extremely correlative with MABP in SH R (the values of r were -0.7174), in WKY, the BKCa current density was correlative with MAB P r = -0.4832.</p><p><b>CONCLUSION</b>BKCa current and current density attenuate with aging, the level of blood pressure is response of the attenuated degree. The BKCa current density is extremely correlative with the blood pressure.</p>

Effect of exercise stress on cigarette smoking induced downregulation of BKca and Kv1.5 expression in pulmonary arterial smooth muscle cells of rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of exercise stress on chronic cigarette smoking induced downregulation of large conductance calcium-activated potassium channel (BKca) and voltage-dependent delayed rectifier potassium channel (Kv1.5) expression in pulmonary arterial smooth muscle cells of rats.</p><p><b>METHODS</b>Rats were divided into three groups: the normal control group, the smoking control group and the smoking + exercise group. The plasma cortisol level, the potassium channel expression and the pathological changes in lung tissue were determined with HE staining, the immunohistochemistry and the in-situ hybridization.</p><p><b>RESULTS</b>(1) In the smoking + exercise group, the plasma cortisol level was determined immediately after exercise [(1528.7 +/- 469.7) ng/L] and was higher than that determined before exercise [(672.4 +/- 235.7) ng/L] (P < 0.01); (2) The HE staining showed that the chronic pulmonary inflammatory response in the smoking control group was severe while it was mild in the smoking + exercise group; (3) The mRNA and protein expression (OD value) of BKca in the smoking control group (mRNA: 0.2206 +/- 0.0415 for big artery and 0.3935 +/- 0.1378 for small artery; protein: 0.2634 +/- 0.1219 for big artery and 0.0995 +/- 0.0851 for small artery) were less than those in the normal control group. The mRNA expression of BKca in the smoking + exercise group (OD value) (0.5022 +/- 0.1134 for big artery and 0.6408 +/- 0.2135 for small artery) was higher than that in the smoking control group; (4) The mRNA and protein expression of Kv1.5 in the smoking control group (OD value) (mRNA: 0.9354 +/- 0.3290 for big artery and 0.5012 +/- 0.1170 for small artery; protein: 1.1112 +/- 0.3310 for big artery and 0.4736 +/- 0.1250 for small artery) were less than those in the normal control group. The protein expression of Kv1.5 in the smoking + exercise group (0.7445 +/- 0.2690) in small artery was higher than that in the smoking control group.</p><p><b>CONCLUSION</b>Proper exercise stress can decrease inhibition effect of the chronic smoking on the expression of potassium channel BKca and Kv1.5, which perhaps partly results from exercise induced increase of cortisol secretion.</p>