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The Journal of Neuroscience, October 5, 2005, 25(40):9185-9194; doi:10.1523/JNEUROSCI.2858-05.2005
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Cellular/Molecular
Functional Role of the Fast Transient Outward K+ Current IA in Pyramidal Neurons in (Rat) Primary Visual Cortex
Weilong Yuan,1
Andreas Burkhalter,2 and
Jeanne M. Nerbonne1
Departments of 1Molecular Biology and Pharmacology and 2Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri 63110
A molecular genetic approach was exploited to directly test the hypothesis that voltage-gated K+ (Kv) channel pore-forming ( ) subunits of the Kv4 subfamily encode the fast transient outward K+ current (IA) in cortical pyramidal neurons and to explore the functional role of IA in shaping action potential waveforms and in controlling repetitive firing in these cells. Using the biolistic gene gun, cDNAs encoding a mutant Kv4.2 subunit (Kv4.2W362F), which functions as a dominant negative (Kv4.2DN), and enhanced green fluorescent protein (EGFP) were introduced in vitro into neurons isolated from postnatal rat primary visual cortex. Whole-cell voltage-clamp recordings obtained from EGFP-positive pyramidal neurons revealed that IA is selectively eliminated in cells expressing Kv4.2DN. The densities and properties of the other Kv currents are unaffected. In neurons expressing Kv4.2DN, input resistances are increased and the (current) thresholds for action potential generation are decreased. In addition, action potential durations are prolonged, the amplitudes of afterhyperpolarizations are reduced, and the responses to prolonged depolarizing inputs are altered markedly in cells expressing Kv 4.2DN. At low stimulus intensities, firing rates are increased in Kv4.2DN-expressing cells, whereas at high stimulus intensities, Kv4.2DN-expressing cells adapt strongly. Together, these results demonstrate that Kv4 subunits encode IA channels and that IA plays a pivotal role in shaping the waveforms of individual action potentials and in controlling repetitive firing in visual cortical pyramidal neurons.
Key words: Kv channels; Kv4.2DN; gene gun; neuronal excitability; repetitive firing; remodeling
Received April 26, 2005;
revised August 12, 2005;
accepted August 16, 2005.
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