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Voltage gating of the Shaker potassi...

Sack, Jon Thomas.

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Voltage gating of the Shaker potassium channel is modified by 6-bromo-2-mercaptotryptamine, a novel gastropod toxin.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Voltage gating of the Shaker potassium channel is modified by 6-bromo-2-mercaptotryptamine, a novel gastropod toxin./
作者:	Sack, Jon Thomas.
面頁冊數:	86 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4223.
Contained By:	Dissertation Abstracts International64-09B.
標題:	Biology, Neuroscience. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3104138
ISBN:	0496517063

Voltage gating of the Shaker potassium channel is modified by 6-bromo-2-mercaptotryptamine, a novel gastropod toxin.
Sack, Jon Thomas.

Voltage gating of the Shaker potassium channel is modified by 6-bromo-2-mercaptotryptamine, a novel gastropod toxin. - 86 p.

Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4223.

Thesis (Ph.D.)--Stanford University, 2003.

A novel potassium channel antagonist was purified from a defensive mucus secreted by Calliostoma canaliculatum, a marine gastropod. The active compound was found to be a disulfide-linked dimer of 6-bromo-2-mercaptotryptamine (BrMT). Voltage-clamp experiments with ShakerBDelta K channels reveal that extracellular BrMT slows macroscopic activation and reduces peak K conductance but has no effect on deactivation kinetics. The reduction of peak K conductance by BrMT is linked to C-type inactivation. Analysis of single channel activity indicates that the latency to first opening is greatly prolonged by BrMT, but unitary conductance and bursting behavior once a channel opens are essentially normal. Paralleling its effects against ionic current activation, BrMT greatly reduces peak amplitude and slows kinetics of ON gating currents. In contrast, OFF gating currents are not altered by BrMT, indicating that all of the channel's gating machinery remains operative in the presence of BrMT. The Shaker gating mutant V369I;I372L;S376T separates early and later gating steps into distinct voltage ranges and was used to distinguish which subsets of gating steps are affected by BrMT. BrMT slows transitions through early gating steps while appearing to leave later steps unaltered. This novel toxin thus inhibits activation of Shaker channels by specifically slowing movement of their voltage sensors, thereby hindering channel opening early in the activation pathway. The sigmoidicity of the activation kinetics of Shaker K channels in BrMT suggests that BrMT slows a step that is cooperative among channel subunits. BrMT was tested for activity against a variety of voltage-gated K channel subtypes. Unlike the activity seen against Shaker K channels, 10 muM BrMT did not inhibit Kv2.1 (drk1) and chimeras between Kv2.1 and Shaker K channels were used to localize the site of action by BrMT.

ISBN: 0496517063Subjects--Topical Terms:

1017680
Biology, Neuroscience.

Voltage gating of the Shaker potassium channel is modified by 6-bromo-2-mercaptotryptamine, a novel gastropod toxin.
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