The Spark of Life – Book Review

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I had the great pleasure in late October to attend the awarding of the Lewis Thomas Prize for Writing about Science to Dr Frances Ashcroft for her book The Spark of Life. The ceremony included a lecture by the author followed by a dinner at the Rockefeller University President’s  house and further discussion with the … Continue reading

The importance of charge compensation in the membrane

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In this post I continue my series on the omega current by discussing how a mutation that removes a charged group from the voltage-sensor domain (VSD) would be highly destabilizing and disruptive. The omega current is a leak current that passes through the VSD of mutated voltage-gated cation channels. In some cases, the mutated channels … Continue reading

Omega Current Channelopathies

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In this post I will be continuing my series on the omega current. The omega current is a leak current that passes through the voltage-sensor domain (VSD) of mutated voltage-gated cation channels. Mutation of the VSD S4 helix can reveal a cryptic pore that allows ions (H+, Li+, K+, Rb+ and even guanidinium) to cross … Continue reading

The Omega Current

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Mutation of voltage-sensor domains (VSDs) can sometimes lead to ions leaking across the membrane through the VSDs themselves. Ion conduction through the mutated VSD of the Shaker Kv channel was coined the “omega current” by Tombola, Pathak and Isacoff (Tombola et al., 2005). Many different mutations have been identified that result in current leaking through the VSDs of … Continue reading

The Problem of Aligning S4

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Recently, a number of papers have come out that have used sequence homology to generate structural models of human Hv1 (Musset et al,. 2010; Ramsey et al., 2010; Wood et al., 2012). These models have then been used for docking and molecular-dynamics simulations to try to extract some mechanistic insight into the channel function. In … Continue reading

The Mechanism of Voltage Gating in Potassium Channels? – Part 2 Activation

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OK, time for part 2. If you missed part 1 of this two post series check it out here. Just to recap, I am discussing the recent Science paper (April 13th issue) from the D.E. Shaw Research group, entitled “The Mechanism of Voltage Gating in Potassium Channels.” In this paper, Jensen et al. use their … Continue reading

The Mechanism of Voltage Gating in Potassium Channels? – Part 1 Deactivation

chimera

In this two part post I will discuss the recent Science paper (April 13th issue) from the D.E. Shaw Research group, entitled “The Mechanism of Voltage Gating in Potassium Channels.” In this paper Jensen et al. use their custom designed supercomputer Anton (named after Anton von Leeuwenhoek, the 18th century microscopist) to perform molecular dynamics … Continue reading