Referenced in: none

Automatically associated channels: Kir6.1 , Kir6.2

Title: K(ATP) channel openers in the trigeminovascular system.

Authors: K B Ploug, D V Amrutkar, M Baun, R Ramachandran, A Iversen, T M Lund, S Gupta, A Hay-Schmidt, J Olesen, I Jansen-Olesen

Journal, date & volume: Cephalalgia, 2012 Jan , 32, 55-65

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22144717

Abstract
The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involves opening of vascular or neuronal K(ATP) channels and mast cell degranulation. Using rat as a model, we studied the molecular presence of K(ATP) channels in the trigeminovascular system. Furthermore, we examined whether K(ATP) channel openers stimulate the in vitro release of CGRP and whether they degranulate dural mast cells.mRNA and protein expression of K(ATP) channel subunits were studied in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) by qPCR and western blotting. In vitro CGRP release was studied after application of levcromakalim (1 µM) and diazoxide (10 µM) to freshly isolated rat dura mater, TG and TNC. Rat dural mast cells were challenged in situ with levcromakalim (10(-5) M) to study its potential degranulation effect.mRNA and protein of K(ATP) channel subunits Kir6.1, Kir6.2, SUR1 and SUR2B were identified in the TG and TNC. K(ATP) channel openers did not release or inhibit capsaicin-induced CGRP release from dura mater, TG or TNC. They did also not induce dural mast cell degranulation.K(ATP) channel openers do not interact with CGRP release or mast cell degranulation. Activation of these channels in the CNS is antinociceptive and therefore cannot explain the headache induced by K(ATP) channel openers. Thus, they are likely to induce headache by interaction with extracerebral K(ATP) channels, probably the SUR2B isoforms.