Open AccessPolymodal Mechanism for TWIK-Related K+ Channel Inhibition by Local Anesthetic
Author(s) -
Mahmud Arif Pavel,
Hae-Won Chung,
Erling N. Petersen,
Scott B. Hansen
Publication year - 2019
Publication title -
anesthesia and analgesia/anesthesia and analgesia
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.404
H-Index - 201
eISSN - 1526-7598
pISSN - 0003-2999
DOI - 10.1213/ane.0000000000004216
Subject(s) - local anesthetic , tetracaine , biophysics , potassium channel , anesthetic , ion channel , medicine , anesthesia , pharmacology , biochemistry , chemistry , lidocaine , biology , receptor
Local anesthetics cause reversible block of pain and robustly inhibit TWIK-related K channel (TREK-1) currents. Before local anesthesia onset, injection of local anesthetics can cause unwanted transient pain. TREK-1 is an anesthetic-sensitive potassium channel that when inhibited produces pain. A disordered C-terminal loop of TREK-1 is thought to contribute to anesthetic sensitivity, but the molecular basis for TREK-1 inhibition by local anesthetics is unknown. Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA) required for TREK-1 activation and also binds to the channel's C terminus.