The M-type K+ current was first described in sympathetic ganglia cells as a voltage-gated non-inactivating conductance which is strongly suppressed by stimulation of muscarinic acetylcholine receptors. the voltage-threshold of gating near typical neuronal resting potentials and the slow kinetics of activation and deactivation of the M-current provides a powerful mechanism for the regulation of neuronal excitability. Modulation of the M-current exerts profound effect on the action potential initiation, firing frequency, and general neuronal discharge properties. However, although a number of investigators have characterized the impact of M-current activity on neuronal discharge properties, it has not yet been established if the resultant influence on release of neurotransmitter is also due to localized M-channel action at release sites which further tune the neurotransmitter released per arriving action potential. Studies using synaptosomes prepared from hippocampal nerve terminals and using slice recordings suggest such a direct link between the M-current and neurotransmitter release. Previous somatic recordings from hippocampal neurons have indicated that the KCNQ current is involved in determining several aspects of neuronal excitability, including the resting membrane potential (RMP), spike frequency adaptation, and burst suppression. These studies combined lead to the hypothesis that G-protein signaling pathways directly tune the release of neurotransmitter from nerve terminal via control of M-channel, and resultant regulation of presynaptic membrane potential.the knowledge of the role of M-channels in neuronal activity will allow a possible design of new modes of therapeutic intervention for multiple diseases.