Referenced in: none

Automatically associated channels: Kv1.5 , Slo1

Title: Activation of vascular smooth muscle K+ channels by endothelium-derived relaxing factors.

Authors: G J Waldron, W C Cole

Journal, date & volume: Clin. Exp. Pharmacol. Physiol., 1999 Feb , 26, 180-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10065344

Abstract
1. Endothelium-derived relaxing factors (EDRF), including nitric oxide (NO), prostacyclin (PGI2) and an as yet uncharacterized endothelium-derived hyperpolarizing factor (EDHF), are now recognized to induce relaxation of vascular smooth muscle, in part via the activation of K+ channels. 2. Experiments using selective K+ channel blockers, including iberiotoxin (IbTX), glibenclamide, apamin and 4-aminopyridine (4-AP) to inhibit endothelium-induced relaxation suggest that more than one type of K+ channel may be involved, depending on the species and tissue, including: (i) large conductance Ca(2+)-activated (BKCa) channels; (ii) ATP-sensitive (KATP) channels; (iii) small conductance Ca(2+)-activated (SKCa) channels; and (iv) voltage-gated (Kv) K+ channels. 3. Recent observations suggest a role for Kv channels in some vessels based on a sensitivity of NO- and PGI2-mediated relaxations to 4-AP, as well as a complete suppression of EDHF-dependent relaxation by a combination of charybdotoxin (ChTX) and apamin but not IbTX and apamin. 4. The molecular identity of the K+ channels affected by EDRF is not well characterized. Recently, findings indicate that the pore-forming alpha-subunit tetramers of vascular smooth muscle BKCa channels are due to the expression of the so-called Slo channel gene. The identities of the KATP, SKCa and Kv channels involved in endothelium-dependent vasodilation are not known. 5. The component of whole-cell Kv current affected by PGI2 may be due to slowly inactivating, 4-AP-sensitive, 15 pS delayed-rectifier K+ channels (KDR); the activity of these channels in vascular myocytes is increased by forskolin and protein kinase A (PKA) and rabbit portal vein Kv1.5 pore-forming alpha-subunits, which appear to be a component of native KDR current and possess consensus phosphorylation sequences for PKA.