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Small Conductance (small + conductance)
Selected AbstractsHuman Bone Cell Hyperpolarization Response to Cyclical Mechanical Strain Is Mediated by an Interleukin-1, Autocrine/Paracrine LoopJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2000D. M. Salter Abstract Mechanical stimuli imparted by stretch, pressure, tension, fluid flow, and shear stress result in a variety of biochemical responses important in bone (re)modeling. The molecules involved in the recognition and transduction of mechanical stimuli that lead to modulation of bone cell function are not yet fully characterized. Cyclical pressure-induced strain (PIS) induces a rapid change in membrane potential of human bone cells (HBC) because of opening of membrane ion channels. This response is mediated via integrins and requires tyrosine kinase activity and an intact actin cytoskeleton. We have used this electrophysiological response to further study the signaling events occurring early after mechanical stimulation of HBC. Stimulation of HBC at 0.33Hz PIS, but not 0.104 Hz PIS, results in the production of a transferable factor that induces membrane hyperpolarization of unstimulated HBC. The production of this factor is inhibited by antibodies to ,1-integrin. Interleukin-1, (IL-1,) and prostaglandin E2 (PGE2) were identified as candidate molecules for the transferable factor as both were shown to induce HBC hyperpolarization by opening of small conductance calcium-activated potassium channels, the means by which 0.33 Hz PIS causes HBC hyperpolarization. Antibodies to IL-1,, but not other cytokines studied, inhibit the hyperpolarization response of HBC to 0.33 Hz PIS. Comparison of the signaling pathways required for 0.33 Hz PIS and IL-1,-induced membrane hyperpolarization shows that both involve the phospholipase C/inositol triphosphate pathway, protein kinase C (PKC), and prostaglandin synthesis. Unlike 0.33 Hz PIS-induced membrane hyperpolarization, IL-1,-induced hyperpolarization does not require tyrosine kinase activity or an intact actin cytoskeleton. These studies suggest that 0.33 Hz PIS of HBC induces a rapid, integrin-mediated, release of IL-1, with a subsequent autocrine/paracrine loop resulting in membrane hyperpolarization. IL-1, production in response to mechanical stimuli is potentially of importance in regulation of bone (re)modeling. [source] Calcium-activated potassium channels and endothelial dysfunction: therapeutic options?BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2009Michel Félétou The three subtypes of calcium-activated potassium channels (KCa) of large, intermediate and small conductance (BKCa, IKCa and SKCa) are present in the vascular wall. In healthy arteries, BKCa channels are preferentially expressed in vascular smooth muscle cells, while IKCa and SKCa are preferentially located in endothelial cells. The activation of endothelial IKCa and SKCa contributes to nitric oxide (NO) generation and is required to elicit endothelium-dependent hyperpolarizations. In the latter responses, the hyperpolarization of the smooth muscle cells is evoked either via electrical coupling through myo-endothelial gap junctions or by potassium ions, which by accumulating in the intercellular space activate the inwardly rectifying potassium channel Kir2.1 and/or the Na+/K+ -ATPase. Additionally, endothelium-derived factors such as cytochrome P450-derived epoxyeicosatrienoic acids and under some circumstances NO, prostacyclin, lipoxygenase products and hydrogen peroxide (H2O2) hyperpolarize and relax the underlying smooth muscle cells by activating BKCa. In contrast, cytochrome P450-derived 20-hydroxyeicosatetraenoic acid and various endothelium-derived contracting factors inhibit BKCa. Aging and cardiovascular diseases are associated with endothelial dysfunctions that can involve a decrease in NO bioavailability, alterations of EDHF-mediated responses and/or enhanced production of endothelium-derived contracting factors. Because potassium channels are involved in these endothelium-dependent responses, activation of endothelial and/or smooth muscle KCa could prevent the occurrence of endothelial dysfunction. Therefore, direct activators of these potassium channels or compounds that regulate their activity or their expression may be of some therapeutic interest. Conversely, blockers of IKCa may prevent restenosis and that of BKCa channels sepsis-dependent hypotension. Mandarin translation of abstract [source] Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channelsBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001J Grainger The effects of the endocannabinoid, anandamide, and its metabolically stable analogue, methanandamide, on induced tone were examined in sheep coronary artery rings in vitro. In endothelium-intact rings precontracted to the thromboxane A2 mimetic, U46619, anandamide (0.01 , 30 ,M) induced slowly developing concentration-dependent relaxations (pEC50 [negative log of EC50]=6.1±0.1; Rmax [maximum response]=81±4%). Endothelium denudation caused a 10 fold rightward shift of the anandamide concentration-relaxation curve without modifying Rmax. Methanandamide was without effect on U46619-induced tone. The anandamide-induced relaxation was unaffected by the cannabinoid receptor antagonist, SR 141716A (3 ,M), the vanilloid receptor antagonist, capsazepine (3 and 10 ,M) or the nitric oxide synthase inhibitor, L -NAME (100 ,M). The cyclo-oxygenase inhibitor, indomethacin (3 and 10 ,M) and the anandamide amidohydrolase inhibitor, PMSF (70 and 200 ,M), markedly attenuated the anandamide response. The anandamide transport inhibitor, AM 404 (10 and 30 ,M), shifted the anandamide concentration-response curve to the right. Precontraction of endothelium-intact rings with 25 mM KCl attenuated the anandamide-induced relaxations (Rmax=7±7%), as did K+ channel blockade with tetraethylammonium (TEA; 3 ,M) or iberiotoxin (100 nM). Blockade of small conductance, Ca2+ -activated K+ channels, delayed rectifier K+ channels, KATP channels or inward rectifier K+ channels was without effect. These data suggest that the relaxant effects of anandamide in sheep coronary arteries are mediated in part via the endothelium and result from the cellular uptake and conversion of anandamide to a vasodilatory prostanoid. This, in turn, causes vasorelaxation, in part, by opening potassium channels. British Journal of Pharmacology (2001) 134, 1003,1012; doi:10.1038/sj.bjp.0704340 [source] The pharmacology of hSK1 Ca2+ -activated K+ channels expressed in mammalian cell linesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000M Shah The pharmacology of hSK1, a small conductance calcium-activated potassium channel, was studied in mammalian cell lines (HEK293 and COS-7). In these cell types, hSK1 forms an apamin-sensitive channel with an IC50 for apamin of 8 nM in HEK293 cells and 12 nM in COS-7 cells. The currents in HEK293 cells were also sensitive to tubocurarine (IC50=23 ,M), dequalinium (IC50=0.4 ,M), and the novel dequalinium analogue, UCL1848 (IC50=1 nM). These results are very different from the pharmacology of hSK1 channels expressed in Xenopus oocytes and suggest the properties of the channel may depend on the expression system. Our findings also raise questions about the role of SK1 channels in generating the apamin-insensitive slow afterhyperpolarization observed in central neurones. British Journal of Pharmacology (2000) 129, 627,630; doi:10.1038/sj.bjp.0703111 [source] Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cellsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2003Kar-Lok Wong Summary 1.,Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2.,In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ([Ca2+]i) was investigated in cultured vascular smooth muscle (A7r5) cells using the Ca2+ -sensitive dye Fura-2 as an indicator. 3.,The increase in [Ca2+]i in A7r5 cells produced by vasopressin (1 µmol/L) or phenylephrine (1 µmol/L) was attenuated by TMP in a concentration-dependent manner. Only inhibitors specific to ATP-sensitive potassium (KATP) channels or small conductance calcium-activated potassium (SKCa) channels attenuated the action of TMP (10 µmol/L) on [Ca2+]i. However, blockers of other K+ channels failed to modify the inhibitory action of TMP (10 µmol/L) on [Ca2+]i. 4.,The action of TMP on membrane potential in A7r5 cells was monitored by the fluorescence of bisoxonol. Tetramethylpyrazine caused a concentration-dependent inhibition of changes in membrane potential elicited by KCl (20 mmol/L) or phenylephrine (1 µmol/L), an effect that was totally reversed by glibenclamide (100 µmol/L) and apamin (100 nmol/L) in combination. 5.,The results obtained indicate that the decrease in [Ca2+]i in A7r5 cells produced by TMP is mediated mainly by opening of KATP and/or SKCa channels. [source] | ||||||||||