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Kv1.1-Containing Channels Are Critical for Temporal Precision During Spike Initiation

¹Neurobiology and Behavior Program, University of Washington; and ²Departments of Otolaryngology-HNS and Pharmacology and ³the Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington

Submitted 25 January 2005; accepted in final form 15 April 2006

Low threshold, voltage-gated potassium currents (I_kl) are widely expressed in auditory neurons that can fire temporally precise action potentials (APs). In the medial nucleus of the trapezoid body (MNTB), channels containing the K_v1.1 subunit (encoded by the Kcna1 gene) underlie I_kl. Using pharmacology, genetics and whole cell patch-clamp recordings in mouse brain slices, we tested the role of I_kl in limiting AP latency-variability (jitter) in response to trains of single inputs at moderate to high stimulation rates. With dendrotoxin-K (DTX-K, a selective blocker of K_v1.1-containing channels), we blocked I_kl maximally (80% with 100 nM DTX-K) or partially (50% with 1-h incubation in 3 nM DTX-K). I_kl was similar in 3 nM DTX-K–treated cells and cells from Kcna1^–/– mice, allowing a comparison of these two different methods of I_kl reduction. In response to current injection, I_kl reduction increased the temporal window for AP initiation and increased jitter in response to the smallest currents that were able to drive APs. While 100 nM DTX-K caused the largest increases, latency and jitter in Kcna1^–/– cells and in 3 nM DTX-K–treated cells were similar to each other but increased compared with +/+. The near-phenocopy of the Kcna1^–/– cells with 3 nM DTX-K shows that acute blockade of a subset of the K_v1.1-containing channels is functionally similar to the chronic elimination of all K_v1.1 subunits. During rapid stimulation (100–500 Hz), I_kl reduction increased jitter in response to both large and small inputs. These data show that I_kl is critical for maintaining AP temporal precision at physiologically relevant firing rates.

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