Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M-1 muscarinic acetylcholine receptors

1. KCNQ1-4 potassium channels were expressed in mammalian Chinese hamster o vary (CHO) cells stably transfected with M-1 muscarinic acetylcholine recep tors and currents were recorded using the whole-cell perforated patch techn ique 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 individu ally and also those produced by KCNQ2+KCNQ3 and KCNQ1+KCNE1 heteromers, whi ch are thought to generate neuronal M-currents (I-K,I-M) and cardiac slow d elayed rectifier currents (I-K,I-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, re quires a diffusible second messenger.