The motor cortex generates synchronous network oscillations at frequencies between 7-14 Hz during disinhibition or low [Mg++]o buffers, but the underlying mechanisms are poorly understood. These oscillations, termed here ~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 ~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 ~10 Hz oscillations. Interestingly, drugs known to suppress the persistent sodium current abolished ~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 ~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 ~10 Hz oscillations of excitatory motor cortex networks.