Loss Of Regulation Of Primary Afferent Neuronal KATP Channels By Calcium-Calmodulin- CaMKII Mediates Hyperalgesia After SNL

Abstract

To test the hypothesis that the arginine mutation affects permeation by inhibiting conduction through the pore due to its size and charge, we generated double mutant G156R/N160D channels. Double mutant channels were functional; in addition, G156R/N160D did not show strong rectification in contrast to N160D, suggesting electrostatic interaction between the two residues. Single channel activity of double mutant channels exhibit altered intraburst gating kinetics compared to WT, suggesting the mutations or their interaction affects the selectivity filter. However, double mutant channels were sensitive to inhibitor ATP and activators MgADP and long-chain acyl Coenzyme A similar to WT channels. Collectively, our results demonstrate functional rescue of the putative glycine hinge position caused by a disease mutation in KATP channels.