title: Putative M-type potassium channels in neuroblastoma-glioma hybrid cells: inhibition by muscarine and bradykinin.
abstract: Putative M-type K(+)-channels ('M-channels') were recorded in differentiated NG108-15 neuroblastoma x glioma hybrid cells transformed to express m1 muscarinic acetylcholine receptors using cell-attached patch-electrodes. Channels showed multiple conductances, with peaks at 6-9 and 12-15 pS. Averaged currents showed time-dependent activation during 1 s depolarization steps to around -30 mV. Steady-state Po increased in a voltage-dependent manner when the membrane was depolarized between 10 and 60 mV, with a limiting slope of 5.5 mV/e-fold change in Po. Steady-state kinetics were fit by two open and three shut times: depolarization shortened shut times and lengthened open times. Application of muscarine (10 microM) or bradykinin (10 microM) to the membrane outside the patch reversibly reduced steady-state in-patch channel activity to 38.4 +/- 11.7 and 28.8 +/- 6.1% of control values, respectively. Inhibition was accompanied by a lengthening of channel shut times without significant change in open times or distribution of conductance levels. No effect of muscarine or bradykinin on whole-cell or membrane patch delayed rectifier currents was detected. It is concluded that M-channels in NG108-15 cells are qualitatively similar to, but sparser than, those previously reported in rat sympathetic neurones. Their inhibition by extra-patch acetylcholine and bradykinin suggests that a mobile messenger is involved in the transduction process leading from receptor activation to channel closure.
authors.affiliation: Department of Pharmacology, University College London, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Selyanko
authors.forename: J
authors.initials: J
authors.lastname: Robbins
authors.forename: D A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002461:Cell Line, Transformed; D005910:Glioma / Q000378:metabolism* / Q000503:physiopathology; D006822:Hybrid Cells; D015640:Ion Channel Gating; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009116:Muscarine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism* / Q000503:physiopathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013552:Swine
chemical_list: D018721:Muscarinic Agonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012333:RNA, Messenger; D009116:Muscarine; D001920:Bradykinin