Voltage gated """"""""delayed rectifier"""""""" potassium channels in excitable cells are important for rapid repolarization of the membrane during an action potential. Delayed rectifiers slowly inactivate during maintained depolarization, however (in some cases) inactivation develops quite rapidly during a train of action potential-like pulses. The time- and voltage-dependence of inactivation profoundly affects the behavior of a neuron, and could potentially be related to a number of neurological disorders that involve abnormal neuronal excitability, such as epilepsy. There are three specific aims of this work: (1) to determine the nature and extent of several types of inactivation that may occur in a particular delayed rectifier, Kv2.1, (2) to determine how inactivation is coupled to gating in Kv2.1, and (3) to apply that information to the study of native delayed rectifiers in thalamic neurons.
Those aims will be accomplished by conducting whole cell voltage clamp recordings in cultured HEK293 cells transfected with Kv2.
1 (Aims 1 and 2), or in acutely dissociated ventrobasal thalamic neurons from rat (Aim 3). These experiments will contribute significantly to our long-term objectives of understanding both the mechanism of ion channel function and the contribution of that function to neuronal activity.
