Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Ion Selectivity in Some Cation Channels
We unambiguously expose and explain why and how a given cation-channel (KcsA, NavRh and the L-type Cav) are highly selective with conductance of the order of one million ions per second. The correct physico-biochemical mechanisms responsible for the high selectivity consist of five conditions---(i) optimum dehydration energy (a1), (ii) high concentration of the correct ion (a2), (iii) Ramachandran attraction (stronger than the strongest van der Waals type attraction) (a3), (iv) proper pore and ionic sizes (a4), and (v) high ion conductance within the selectivity pore (b5).
Here, (a1) to (a4) are activated before the cations could enter the selectivity pore, in other words, (a1) to (a4) which cation can enter the selectivity pore with the highest probability. While (b5) captures the ion selectivity indirectly within the selectivity filter (when the cations are within the selectivity pore). The reason why (b5) is only indirectly responsible for ion selectivity is because the incorrect cations are never ejected out of the pore (means, out of the cell, not into the cell), once they are found to be within the filter. Therefore, (b5) is associated to these well known criteria---thermodynamic stability and the knock-on permeation mechanism, which determine the ion conductance within the selectivity pore. Here, we have selected KcsA, NavRh and Cav (L-type) cation channels because we know these properties precisely, for example, the pore size, ion conductance for different ions, and the residue types within the selectivity filter. Therefore, we cannot apply the theory to an arbitrary ion channel without first establishing the above parameters.
Our analytic theory complements the results from previous computational models, and also exposes two new information, in particular, ion selection is actually activated even before the ions enter a particular cation channel pore, as well as the microscopic physics responsible for ion conductance for different types of cations in different cation channels. The generalized conditions play their crucial roles simultaneously in selecting the correct ions to enter the selectivity pore (due to (a1) to (a4)) and also allowing the ions to permeate through the selectivity pore with maximum conductance (due to (b5)). Our approach makes extensive use of the laws of quantum physics, particularly, the atomic and molecular energy-level spacings, excitation probability, electron-electron repulsion and the Ramachandran attraction. This work was supported by Sebastiammal Savarimuthu, Arulsamy Innasimuthu, Arokia Das Anthony, Amelia Das Anthony, Malcolm Anandraj and Kingston Kisshenraj. Partial financial assistance came from Kurunathan Ratnavelu through the University of Malaya research grant No. RG089/10AFR (from 18 June 2012 to 17 September 2012).
Ramachandran, G. N., Sasisekharan, V., & Ramakrishnan, C. (1963). Stereochemistry of polypeptide chain configurations. Journal of Molecular Biology, 7, 95-99.
Andrew Das Arulsamy
Condensed Matter Group