Multiphasic profiles for voltage-dependent K+ channels: Reanalysis of data of MacKinnon and coworkers

TL;DR

This study reanalyzes voltage-dependent K+ channel data, revealing that multiphasic profiles with straight-line segments and jumps better fit the data than traditional Boltzmann functions, challenging conventional interpretations.

Contribution

It demonstrates that ion channel data are more accurately represented by multiphasic profiles rather than curvilinear models like Boltzmann functions.

Findings

Multiphasic profiles fit the data significantly better than Boltzmann functions.

Many profiles show discontinuous jumps between linear segments.

High correlation coefficients support the multiphasic model's accuracy.

Abstract

In a study of the role that voltage-dependent K+ channels may have in the mechanosensation of living cells (Schmidt et al. Proc Soc Natl Acad Sci USA 109: 10352-10357. 2012), the data were as conventionally done fitted by a Boltzmann function. However, as also found for other data for ion channels, this interpretation must be rejected in favor of a multiphasic profile, a series of straight lines separated by discontinuous transitions, quite often in the form of noncontiguities (jumps). The data points in the present study are often very unevenly distributed around the curvilinear profiles. Thus, for 43 of the 75 profiles, the probability is less than 5% that the uneven distribution is due to chance, for 26 the probability is less than 1%, and for 12 the probability is less than 0.1%, giving a vanishingly low overall probability for all profiles. Especially at low voltages, the differences between the fits to curvilinear and multiphasic profiles may be huge. In the multiphasic profiles, adjacent lines are quite often parallel or nearly so, in which case the transitions are, necessarily, in the form of jumps. The lines in the multiphasic profiles appear to be perfectly straight, with no indication of any curvilinearity. The r values are for the most part high, quite often exceedingly high. In addition to activation of ion channels, a wide variety of biological as well as non-biological processes and phenomena involving binding, pH, folding/unfolding and effect of chain length can be well represented by multiphasic profiles (Nissen 2015a,b, 2016. Posted on arXiv.org with Paper ID arXiv: 1511.06601, 1512.02561 and 1603.05144). Introduction