Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion

Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion

Departments of ^*Pharmacology and ^§Surgery/Division of Otolaryngology, Yale University School of Medicine, New Haven, CT 06520; and ^‡Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, NJ 07102

Edited by Masakazu Konishi, California Institute of Technology, Pasadena, CA, and approved December 9, 1997 (received for review October 7, 1997)

Abstract

Spines are specialized neuronal membrane structures, often localized at sites where synaptic information is relayed from one cell to another in the central nervous system. By electron immunomicroscopy we have found that the mammalian Shaw family potassium channel Kv3.1 is localized on spine-like protrusions, adjacent to postsynaptic membranes of bushy cells in the cochlear nucleus. As direct characterization of the electrophysiological behavior of ion channels in such structures is difficult, we have used Kv3.1-transfected CHO cells to create artificial spine-like membrane compartments. Membrane patches were sucked into microelectrodes to form small, cell-attached vesicles with dimensions comparable to those of the neuronal structures. Currents mediated by the Kv3.1 channel in these vesicles undergo rapid and complete inactivation, in contrast to their noninactivating behavior in whole-cell recordings. This apparent inactivation is caused by the rapid depletion of K⁺ from the vesicle and the slow refilling of K⁺ into the vesicle compartment from the bulk cytoplasm. Our data provide evidence that compartmentalized ionic transients can be generated in spine-like membrane structures and support the view that the localization of ion channels in spine-like structures may influence responses to synaptic stimulation.

Footnotes

↵ † Present address: Division of Neurology and The Epilepsy Research Program, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
↵ ¶ To whom reprint requests should be addressed at: Department of Pharmacology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520. e-mail: Kaczmarek{at}yale.edu.
This paper was submitted directly (Track II) to the Proceedings Office.