Michael J. Saganich, MS

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Characterization of Subthreshold-Operating Voltage-Gated K+ Channels in Brain.

Potassium channels that are open at membrane potentials close to the threshold for action potential generation have a major influence on neuronal excitability governing the responsiveness of neurons to incoming inputs. The classical example is the M-current (IM), first described in sympathetic neurons (Brown & Adams, 1980) and later found in central neurons (Brown, 1988; Yamada et al., 1989). IM becomes significant above -60 mV, and thus may influence the resting potential and the input resistance of the cell. The current opposes depolarizing signals, and influences the responsiveness of the cell to synaptic inputs. Moreover, the channels mediating this current (M channels or M-type K+ channels) do not inactivate, contributing K+ current during long depolarizations and producing adaptation in repetitive firing neurons. The inhibition of IM by neurotransmitters and neuropeptides generates slow depolarizing synaptic potentials and mediates increases in excitability.

It was recently shown that the classical M-channel in sympathetic neurons is an heteromeric protein containing Kcnq2 and Kcnq3 subunits (Wang et al., 1998). The eight known members of the EAG family of K+ channel pore forming subunits all express homomeric subthreshold-, or near threshold-operating K+ channels, when expressed in heterologous expression systems. Moreover, similar to IM, some EAG currents do not inactivate, and can contribute an M-like steady outward current during long depolarized potentials. Even for EAG family channels that do display inactivation, a large component of non-inactivating current is present.

To begin to understand the modulation of the excitability of different neuronal populations and to facilitate manipulation of these properties, it is necessary to know the distribution of different EAG and Kcnq2 products in CNS neurons. This knowledge is also necessary to select neuronal populations where the properties and functional roles of native EAG channels might be studied.

My research so far has included the cloning and characterization of new members of the EAG family (Saganich et al., 1999), and the high resolution mapping of the genes responsible for the generation of these subthreshold activating K+ channels (Saganich et al 2000 J. Neurosci in press). My current research focuses on the identification and function of EAG and KCNQ K+ currents using the in vitro slice preparation using voltage and current clamp.

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EAG & KCNQ2/3 Expression Page