title: Stimulation of Ca2+-sensing receptor inhibits the basolateral 50-pS K channels in the thick ascending limb of rat kidney.
abstract: We used the patch-clamp technique to study the effect of changing the external Ca2+ on the basolateral 50-pS K channel in the thick ascending limb (TAL) of rat kidney. Increasing the external Ca2+ concentration from 1 mM to 2 or 3 mM inhibited the basolateral 50-pS K channels while decreasing external Ca2+ to 10 μM increased the 50-pS K channel activity. The effect of the external Ca2+ on the 50-pS K channels was observed only in cell-attached patches but not in excised patches. Moreover, the inhibitory effect of increasing external Ca2+ on the 50-pS K channels was absent in the presence of NPS2390, an antagonist of Ca2+-sensing receptor (CaSR), suggesting that the inhibitory effect of the external Ca2+ was the result of stimulation of the CaSR. Application of the membrane-permeable cAMP analog increased the 50-pS K channel activity but did not block the effect of raising the external Ca2+ on the K channels. Neither inhibition of phospholipase A2 (PLA2) nor suppression of cytochrome P450-ω-hydroxylation-dependent metabolism of arachidonic acid was able to abolish the effect of raising the external Ca2+ on the 50-pS K channels. In contrast, inhibition of phospholipase C (PLC) or blocking protein kinase C (PKC) completely abolished the inhibition of the basolateral 50-pS K channels induced by raising the external Ca2+. We conclude that the external Ca2+ concentration plays an important role in the regulation of the basolateral K channel activity in the TAL and that the effect of the external Ca2+ is mediated by the CaSR which stimulates PLC-PKC pathways. The regulation of the basolateral K channels by the CaSR may be the mechanism by which extracellular Ca2+ level modulates the reabsorption of divalent cations.
authors: Department of Pharmacology, Harbin Medical University, Harbin 150086, China.
authors: Shumin
authors: S
authors: Kong
authors: Chengbiao
authors: C
authors: Zhang
authors: Wennan
authors: W
authors: Li
authors: Lijun
authors: L
authors: Wang
authors: Haiyan
authors: H
authors: Luan
authors: Wen-Hui
authors: WH
authors: Wang
authors: Ruimin
authors: R
authors: Gu
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D004963:Estrenes / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000033:anatomy & histology* / Q000378:metabolism*; D008297:Male; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D011760:Pyrrolidinones / Q000378:metabolism; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C569355:2-quinoxaline-carboxamide-N-adamantan-1-yl; D001095:Arachidonic Acids; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011760:Pyrrolidinones; D011810:Quinoxalines; D044169:Receptors, Calcium-Sensing; C081565:arachidonyltrifluoromethane; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000218:Adamantane; D002118:Calcium