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ACTIVATION OF VASCULAR SMOOTH MUSCLE K + CHANNELS BY ENDOTHELIUM‐DERIVED RELAXING FACTORS
Author(s) -
Waldron GJ,
Cole WC
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03006.x
Subject(s) - iberiotoxin , apamin , charybdotoxin , endothelium derived hyperpolarizing factor , chemistry , vascular smooth muscle , biophysics , potassium channel , vasodilation , channel blocker , prostacyclin , calcium activated potassium channel , endothelium , glibenclamide , endocrinology , biochemistry , biology , smooth muscle , organic chemistry , diabetes mellitus , calcium
1. Endothelium‐derived relaxing factors (EDRF), including nitric oxide (NO), prostacyclin (PGI 2 ) 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 (BK Ca ) channels; (ii) ATP‐sensitive (K ATP ) channels; (iii) small conductance Ca 2 + ‐activated (SK Ca ) channels; and (iv) voltage‐gated (K v ) K + channels. 3. Recent observations suggest a role for K v channels in some vessels based on a sensitivity of NO‐ and PGI 2 ‐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 α ‐subunit tetramers of vascular smooth muscle BK Ca channels are due to the expression of the so‐called Slo channel gene. The identities of the K ATP , SK Ca and K v channels involved in endothelium‐dependent vasodilation are not known. 5. The component of whole‐cell K v current affected by PGI 2 may be due to slowly inactivating, 4‐AP‐sensitive, 15 pS delayed‐rectifier K + channels (K DR ); the activity of these channels in vascular myocytes is increased by forskolin and protein kinase A (PKA) and rabbit portal vein K v 1.5 pore‐forming α‐subunits, which appear to be a component of native K DR current and possess consensus phosphorylation sequences for PKA.