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• W2003181636 abstract "1. The pharmacological properties of cationic currents activated by acetylcholine (ACh) (Icat) in guinea-pig ileal smooth muscle cells were investigated, with conventional single patch electrode or nystatin-perforated whole-cell recording. Cs-aspartate was used as the internal solution to allow selective measurement of Icat. 2. Well-known K channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP), procaine and quinine as well as a Ca releasing agent, caffeine, all produced concentration-dependent inhibition of Icat with rapid onset (time constant approximately 100 ms), when applied externally. The recovery from the inhibition on washout also occurred rapidly in the order of 100 ms except in the case of quinine. Approximate values of the half inhibitory concentrations (IC50) were 10 nM for TEA and caffeine, 1-5 mM for 4-AP and procaine, and 1 microM for quinine. The mode of inhibition was voltage-dependent, i.e., depolarization relieved the inhibition with no change in reversal potential. 3. Externally applied diphenylamine-2-carboxylate (DPC) derivatives, DCDPC and flufenamic acid, produced potent inhibition of Icat at micromolar concentrations (IC50s were < 30 microM for DCDPC and 32 microM for flufenamic acid). The onset of and recovery from inhibition occurred slowly and the degree of inhibition depended on the membrane potential only weakly, without any discernible change in the reversal potential. 4. All of the above-tested drugs exhibited comparable inhibitory actions on the voltage-dependent Ca current in the concentration ranges effective at inhibiting Icat. However, amongst them, quinine and flufenamic acid seemed to have several-fold better selectivity for the Icat channel than for the voltage-dependent Ca channel. 5. Internally dialysed GTPgammaS (100 microM) induced inward cationic currents. The effects of drugs on these currents were similar to their effects on the Icat current.6. These results clearly indicate that many drugs used as pharmacological tools in smooth muscle research exert considerable nonspecific effects on various types of channels. The mechanism of inhibition and the relevance to use of these drugs as blockers for the I cat channel are discussed." @default.
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• W2003181636 date "1993-07-01" @default.
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• W2003181636 title "Pharmacological characterization of muscarinic receptor-activated cation channels in guinea-pig ileum" @default.
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• W2003181636 doi "https://doi.org/10.1111/j.1476-5381.1993.tb13644.x" @default.
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