Modulation of Two Transient Potassium Currents in Mouse Hippocampal Neurons

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The individuality of neurons is determined by the particular complement of functional ion channels present in the neuronal membrane. Different neurons express varying numbers of channels selective for sodium, calcium, potassium and chloride ions, and as a consequence have specific patterns of responses to incoming excitatory and inhibitory stimuli. In order to understand how the individuality of neurons is established, a class of potassium currents whose activity influences both the waveform of single action potentials and the pattern of repetitive action potentials will be studied. Experiments will be performed on cultured embryonic mouse hippocampal neurons, a standard preparation for study of early neural development. It has been previously observed that the expression in neurons of two variant forms of transient potassium currents, termed A-current and D-current, is dependent on contact with non-neuronal glial cells. Since A- and D-currents are involved in neuronal electrogenesis, these observations raise the possibility that glial cells modulate neuronal activity by influencing channel expression. To understand how this process might occur, the precise molecular relationship between A- and D-current channels should be clarified. In the present experiments differences in gating and permeation behavior at the single channel level will be examined. Future experiments will focus on issues of gene expression and post-translational modification that may establish the differences between the ion channels underlying A- and D-currents.