Electro-mediated damage in the narrowest pore of voltage-gated K channels in frog skeletal muscle membrane

Abstract

Summary form only given as follows: In addition to electroporation of cell membranes, the authors have also shown shock pulse-induced reduction in voltage-gated ionic channel conductance and channel selectivity, which suggests possible electroconformational changes in proteins of the cell membrane. Therefore, the authors are now attempting to locate the damage in the protein structure. Some of their evidence suggests that the most vulnerable subgroups of channel proteins are located at the narrowest pore of the channels. Experiments were performed using an improved double vaseline-gap voltage and current clamp technique with cut fibers from skeletal muscle of the frog Rana temporaria. The experimental results showed that: 1) the binding of the neurotoxins TIX and TEA on sodium (Na) and potassium (K) channels are not affected by the high voltage electrical shock pulses; 2) the inactivity curve of the delayed rectifier K channel shows little change following electric shock; and 3) K channel conductance and ionic selectivity can be significantly reduced by the electric shock pulse, predicting a depolarization of the membrane resting potential, which has been further proved by directly measuring membrane potential response to an electrical shock. The figure below shows the shock pulse-induced depolarization of the membrane resting potential. Combining these functional alterations of channel proteins, it is possible to answer the question of what subgroups of the channel proteins are the most sensitive to a high voltage electrical shock. The neurotoxin binding sites of TTX and TEA are most likely located on the peripheral residue of the channel proteins not in the narrowest pore of the selectivity filter. Similarly, the well-accepted hypothesis of the channel inactivity suggests that channel inactivity function be correlated to the amino-terminal residues, which are intracellularly located away from the selectivity filter. In contrast, reduction of channel conductance and ionic selectivity are primarily correlated to the narrowest pore of the channels, the selectivity filter. In other words, the narrowest pore of the ion channel with a diameter of a few /spl Aring/ is the most sensitive subgroup to the external electrical field.<>