M-current is a non-inactivating potassium current found in many neuron
al cell types. In each cell type, it is dominant in controlling membra
ne excitability by being the only sustained current in the range of ac
tion potential initiation. It can be modulated by a large array of rec
eptor types, and the modulation can occur either by suppression or enh
ancement. Modulation of M-current has dramatic effects on neuronal exc
itability. This review discusses the numerous second messenger pathway
s that converge on regulation of this current: in particular, two form
s of regulation of the M-current, receptor-mediated modulation and the
control of macroscopic current amplitude by intracellular calcium. Bo
th types of regulation are discussed with reference to the modulation
of single-channel gating properties.