Referenced in: none

Automatically associated channels: Kv10.1 , Slo1

Title: [Pharmacologic analysis of sodium channel inactivation in a nerve fiber membrane]

Authors: B I Khodorov

Journal, date & volume: , 1980 , 12, 317-31

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/6105626

Abstract
Recent advances in the study of the effects of various enzymes, toxins, drugs and ions on Na channels inactivation are reviewed. The available data suggest the protein "inactivation subunit" (IS) to span the membrane. The internal end of this IS protrudes from the membrane to the axoplasm and acts as an inactivation gate (h-gate). It can be affected by intracellular application of some proteases (endopeptidases), protein-specific reagents and drugs, removing (completely or partially) the fast sodium inactivation. The ultraslow sodium inactivation, resistant to proteases, is apparently due to the conformational changes of that part of the channel which is buried in the membrane lipid matrix. The outer end of the IS is provided with chemical groups having a high affinity to anemone and scorpion toxins inducing the modification of Na inactivation when applied from outside the fibre. Batrachotoxin and aconitine cause a simultaneous modification of inactivation, activation and selectivity of Na channels by interacting with a single "receptor site" of the channel. It is proposed that this receptor is disposed in the hydrophobic part of the channel and is allosterically linked with different subunits responsible for the principal channel functions. It is tempting to assume that the batrachotoxin receptor belongs to that subunit which plays a key role in the normal structural interaction of various channel subunits. Inactivation process is critically involved in the voltage- and frequency-dependent inhibition of sodium currents by various quaternary and tertiary amines among which there are local anesthetics and antiarrhythmics.