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. 2017 Jul 12;7:5248. doi: 10.1038/s41598-017-05578-5

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Failure of recovery from inactivation of sodium channels underlies decrease in firing regularity with SK channel inhibition. Shows the availability of sodium channels (ii–iv) during the course of the action potential (i). The number of sodium channels open increased steadily with depolarisation (ii) following the start of the action potential. This was accompanied by a steady increase in the number of inactivated channels (iii). While the number of open channels went back to zero as soon as the action potential had passed, there was a significant difference between the number of channels that remained in the inactivated state (iii). As the channels recovered from inactivation, they became closed (iv); however once again, a large number of channels failed to go into the closed state because they remained inactivated. Shaded region in (A) represents standard deviation around the mean. (B) Although we cannot see a reduction in the number of open channels during the peak of the action potential, there is a small yet statistically significant reduction in the number of open channels during the spike. (C) The reduction in recovery from inactivation is explained by the reduction in the h parameter of sodium channels inactivation dynamics. h was calculated at minimum membrane voltage attained after spike. Error bars represent mean ± S.E.M, not visible due to small errors.