2020
Volume 20, Number 1, pp. 9-15
Physics of biological pacemakers
P.A. Grigoriev
Institute of Cell Biophysics, Russian Academy of Sciences, 142290 Puschino, Moscow Region, Russia
Inactivation of ion-selective conductance is the crucial stage in excitable biological cell membrane activity. Our previous experiments with lipid bilayer membranes containing clusters of the cation-selective channels formed by the 25 kDa protein peroxiredoxin (Prx) have shown that the inactivation of channel conductance is a current- but not voltage-dependent reaction. The clusters-Prx dodecamers-are disintegrated into unitary channels-Prx decamers; the elevated temperature caused by the passage of current through the cluster causes the cluster to disintegrate. It has been discovered that the current generated by the transmembrane concentration gradient of the permeable ions also participates in the inactivation process. It was furthermore discovered that in the absence of current, cluster conductance is restored. Recorded densities of the inactivating current-10-9-10-8 A/μm2-correlate with those reported for excitable biological membranes. The present paper is an attempt to describe the pacemaking activity of the sino-atrial node cell with a molecular model having as its main points: conductance of the membrane ion-channel cluster is inactivated by the heat energy of the current passing through it; the difference in the degree of hydration of the cluster as a total structure from that of the unitary channel outside the cluster results in a difference of their lipid-water partitioning coefficients; the clusters stay in the membrane and the unitary channels leave it; the new cluster is formed inside the cytoplasm from the unitary channels coming out of the cell membrane during the inactivation stage, and the newly assembled cluster enters the membrane during the activation stage; cluster formation kinetics-a colloid coagulation reaction-controls the pacemaker timing.
Keywords: conductance inactivation, ion channel cluster, lipid/water partitioning coefficient, pacemaker activity