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The Journal of Neuroscience, February 15, 2003, 23(4):1133
Modulation of the Kv3.1b Potassium Channel Isoform Adjusts
the Fidelity of the Firing Pattern of Auditory Neurons
Carolyn M.
Macica1,
Christian A. A.
von Hehn1,
Lu-Yang
Wang2,
Chi-Shun
Ho3,
Shigeru
Yokoyama4,
Rolf H.
Joho5, and
Leonard K.
Kaczmarek1
1 Department of Pharmacology, Yale University, New
Haven, Connecticut 06520, 2 Division of Neurology, Hospital
for Sick Children Research Institute, Toronto, Canada,
3 Department of Physiology, University of Michigan Medical
Center, Ann Arbor, Michigan 48109, 4 Department of
Biophysical Genetics, Kanazawa University Graduate School of Medicine,
Kanazawa, Ishikawa, 920-8640, Japan, and 5 Center for Basic
Neuroscience, University of Texas Southwestern Medical Center, Dallas,
Texas 75390
Neurons of the medial nucleus of the trapezoid body, which transmit
auditory information that is used to compute the location of sounds in
space, are capable of firing at high frequencies with great temporal
precision. We found that elimination of the Kv3.1
gene in mice results in the loss of a high-threshold component of
potassium current and failure of the neurons to follow high-frequency stimulation. A partial decrease in Kv3.1 current can be produced in
wild-type neurons of the medial nucleus of the trapezoid body by
activation of protein kinase C. Paradoxically, activation of protein
kinase C increases temporal fidelity and the number of action
potentials that are evoked by intermediate frequencies of stimulation.
Computer simulations confirm that a partial decrease in Kv3.1 current
is sufficient to increase the accuracy of response at intermediate
frequencies while impairing responses at high frequencies. We further
establish that, of the two isoforms of the Kv3.1 potassium channel that
are expressed in these neurons, Kv3.1a and Kv3.1b, the decrease in
Kv3.1 current is mediated by selective phosphorylation of the Kv3.1b
isoform. Using site-directed mutagenesis, we identify a specific
C-terminal phosphorylation site responsible for the observed difference
in response of the two isoforms to protein kinase C activation. Our
results suggest that modulation of Kv3.1 by phosphorylation allows
auditory neurons to tune their responses to different patterns of
sensory stimulation.
Key words:
Kv3.1; potassium channel; MNTB neurons; protein
kinase C; phosphorylation; auditory timing; channel isoforms
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341133-09$05.00/0
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