Cloning of components of a novel subthreshold-activating K+ channel with aunique pattern of expression in the cerebral cortex

Potassium channels that are open at very negative membrane potentials gover n the subthreshold behavior of neurons. These channels contribute to the re sting potential and help regulate the degree of excitability of a neuron by affecting the impact of synaptic inputs and the threshold for action poten tial generation. They can have large influences on cell behavior even when present at low concentrations because few conductances are active at these voltages. We report the identification of a new K+ channel pore-forming sub unit of the ether-a-go-go (Eag) family, named Eag2, that expresses voltage- gated K+ channels that have significant activation at voltages around -100 mV. Eag2 expresses outward-rectifying, non-inactivating voltage-dependent K + currents resembling those of Eag1, including a strong dependence of activ ation kinetics on prepulse potential. However, Eag2 currents start activati ng at subthreshold potentials that are 40-50 mV more negative than those re ported for Eag1. Because they activate at such negative voltages and do not inactivate, Eag2 channels will contribute sustained outward currents down to the most negative membrane potentials known in neurons. Although Eag2 mR NA levels in whole brain appear to be low, they are highly concentrated in a few neuronal populations, most prominently in layer IV of the cerebral co rtex. This highly restricted pattern of cortical expression is unlike that of any other potassium channel cloned to date and may indicate specific rol es for this channel in cortical processing. Layer IV neurons are the main r ecipient of the thalamocortical input. Given their functional properties an d specific distribution, Eag2 channels may play roles in the regulation of the behavioral state-dependent entry of sensory information to the cerebral cortex.