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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 586/14/3493    most recent jphysiol.2008.153734v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Johnston, J. Articles by Forsythe, I. D. PubMed PubMed Citation Articles by Johnston, J. Articles by Forsythe, I. D. Related Collections Neuroscience

¹ MRC Toxicology Unit
² Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, UK

The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K⁺ current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of 37 nS; it is half-activated at –9.2 ± 2.1 mV and half-inactivated at –35.9 ± 1.5 mV. It is blocked by several non-specific potassium channel antagonists including quinine (100 µM) and high concentrations of extracellular tetraethylammonium (TEA; IC₅₀ = 11.8 mM), but no specific antagonists were found. These characteristics are similar to recombinant Kv2-mediated currents. Quantitative RT-PCR showed that Kv2.2 mRNA was much more prevalent than Kv2.1 in the MNTB. A Kv2.2 antibody showed specific staining and Western blots confirmed that it recognized a protein 110 kDa which was absent in brainstem tissue from a Kv2.2 knockout mouse. Confocal imaging showed that Kv2.2 was highly expressed in axon initial segments of MNTB neurons. In the absence of a specific antagonist, Hodgkin–Huxley modelling of voltage-gated conductances showed that Kv2.2 has a minor role during single APs (due to its slow activation) but assists recovery of voltage-gated sodium channels (Nav) from inactivation by hyperpolarizing interspike potentials during repetitive AP firing. Current-clamp recordings during high frequency firing and characterization of Nav inactivation confirmed this hypothesis. We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing.

(Received 12 March 2008; accepted after revision 22 May 2008; first published online 29 May 2008)
Corresponding author I. D. Forsythe: MRC Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK. Email: idf{at}le.ac.uk