The motor cortex generates synchronous network oscillations at frequencies between 7 and 14 Hz during disinhibition or low [Mg2+]o buffers, but the underlying mechanisms are poorly understood. These oscillations, termed here approximately 10 Hz oscillations, are generated by a purely excitatory network of interconnected pyramidal cells because they are robust in the absence of GABAergic transmission. It is likely that specific voltage-dependent currents expressed in those cells contribute to the generation of approximately 10 Hz oscillations. We tested the effects of different drugs known to suppress certain voltage-dependent currents. The results revealed that drugs that suppress the low-threshold calcium current and the hyperpolarization-activated cation current are not critically involved in the generation of approximately 10 Hz oscillations. Interestingly, drugs known to suppress the persistent sodium current abolished approximately 10 Hz oscillations. Furthermore, blockers of K+ channels had significant effects on the oscillations. In particular, blockers of the M-current abolished the oscillations. Also, blockers of both non-inactivating and slowly inactivating voltage-dependent K+ currents abolished approximately 10 Hz oscillations. The results indicate that specific voltage-dependent non-inactivating K+ currents, such as the M-current, and persistent sodium currents are critically involved in generating approximately 10 Hz oscillations of excitatory motor cortex networks.