Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors

1. KCNQ1-4 potassium channels were expressed in mammalian Chinese hamster ovary (CHO) cells stably transfected with M(1) muscarinic acetylcholine receptors and currents were recorded using the whole-cell perforated patch technique and cell-attached patch recording. 2. Stimulation of M(1) receptors by 10 mu M oxotremorine-M (Oxo-M) strongly reduced (to 0-10%) currents produced by KCNQ1-4 subunits expressed individually and also those produced by KCNQ2+KCNQ3 and KCNQ1+KCNE1 heteromers, which are thought to generate neuronal M-currents (I(K,M)) and cardiac slow delayed rectifier currents (I(K,s)), respectively. 3. The activity of KCNQ2+KCNQ3, KCNQ2 and KCNQ3 channels recorded with cell-attached pipettes was strongly and reversibly reduced by Oxo-M applied to the extra-patch membrane. 4. It is concluded that M, receptors couple to all known KCNQ subunits and that inhibition of KCNQ2+KCNQ3 channels, like that of native M-channels, requires a diffusible second messenger.