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The Journal of Neurophysiology Vol. 88 No. 1 July 2002, pp. 394-408
Copyright ©2002 by the American Physiological Society
1Department of Physiology and Neuroscience and Department of Biochemistry, New York University School of Medicine, New York, New York 10016; and 2Department of Neuroscience, Division of Imaging, San Diego, California 92093-0608
Ozaita, A.,
M. E. Martone,
M.
H. Ellisman, and
B. Rudy.
Differential Subcellular Localization of the Two Alternatively
Spliced Isoforms of the Kv3.1 Potassium Channel Subunit in Brain. J. Neurophysiol. 88: 394-408, 2002. Voltage-gated K+ channels containing pore-forming subunits
of the Kv3 subfamily have specific roles in the fast repolarization of
action potentials and enable neurons to fire repetitively at high
frequencies. Each of the four known Kv3 genes encode multiple products
by alternative splicing of 3' ends resulting in the expression of
K+ channel subunits differing only in their C-terminal
sequence. The alternative splicing does not affect the
electrophysiological properties of the channels, and its physiological
role is unknown. It has been proposed that one of the functions of the
alternative splicing of Kv3 genes is to produce subunit isoforms with
differential subcellular membrane localizations in neurons and
differential modulation by signaling pathways. We investigated the role
of the alternative splicing of Kv3 subunits in subcellular localization by examining the brain distribution of the two alternatively spliced versions of the Kv3.1 gene (Kv3.1a and Kv3.1b) with antibodies specific
for the alternative spliced C-termini. Kv3.1b proteins were prominently
expressed in the somatic and proximal dendritic membrane of specific
neuronal populations in the mouse brain. The axons of most of these
neurons also expressed Kv3.1b protein. In contrast, Kv3.1a proteins
were prominently expressed in the axons of some of the same neuronal
populations, but there was little to no Kv3.1a protein expression in
somatodendritic membrane. Exceptions to this pattern were seen in two
neuronal populations with unusual targeting of axonal proteins, mitral
cells of the olfactory bulb, and mesencephalic trigeminal neurons,
which expressed Kv3.1a protein in dendritic and somatic membrane,
respectively. The results support the hypothesis that the alternative
spliced C-termini of Kv3 subunits regulate their subcellular targeting in neurons.
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