Characterization of the potassium channels involved in EDHF-mediated relaxation in cerebral arteries
Petersson, Jesper LU ; Zygmunt, Peter M. LU
and Högestätt, Edward D.
LU
(1997)
In British Journal of Pharmacology
120(7).
p.1344-1350
- Abstract
1. In the presence of N(G)-nitro-L-arginine (L-NOARG, 0.3 mM) and indomethacin (10 μM), the relaxations induced by acetylcholine and the calcium (Ca) ionophore A23187 are considered to be mediated by endothelium-derived hyperpolarizing factor (EDHF) in the guinea-pig basilar artery. 2. Inhibitors of adenosine 5'-triphosphate (ATP)-sensitive potassium (K)-channels (K(ATP); glibenclamide, 10 μM), voltage-sensitive K-channels (K(V); dendrotoxin-I, 0.1 μM or 4-aminopyridine, 1 mM), small (SK(Ca); apamin, 0.1 μM) and large (BK(Ca); iberiotoxin, 0.1 μM) conductance Ca-sensitive K-channels did not affect the L-NOARG/indomethacin-resistant relaxation induced by acetylcholine. 3. Synthetic charybdotoxin (0.1 μM), an inhibitor of BK(Ca), and... (More)
1. In the presence of N(G)-nitro-L-arginine (L-NOARG, 0.3 mM) and indomethacin (10 μM), the relaxations induced by acetylcholine and the calcium (Ca) ionophore A23187 are considered to be mediated by endothelium-derived hyperpolarizing factor (EDHF) in the guinea-pig basilar artery. 2. Inhibitors of adenosine 5'-triphosphate (ATP)-sensitive potassium (K)-channels (K(ATP); glibenclamide, 10 μM), voltage-sensitive K-channels (K(V); dendrotoxin-I, 0.1 μM or 4-aminopyridine, 1 mM), small (SK(Ca); apamin, 0.1 μM) and large (BK(Ca); iberiotoxin, 0.1 μM) conductance Ca-sensitive K-channels did not affect the L-NOARG/indomethacin-resistant relaxation induced by acetylcholine. 3. Synthetic charybdotoxin (0.1 μM), an inhibitor of BK(Ca), and K(V), caused a rightward shift of the concentration-response curve for acetyicholine and reduced the maximal relaxation in the presence of L-NOARG and indomethacin, whereas the relaxation induced by A23187 was not significantly inhibited. 4. A combination of charybdotoxin (0.1 μM) and apamin (0.1 μM) abolished the L-NOARG/indomethacin-resistant relaxations induced by acetylcholine and A23187. However, the acetylcholine-induced relaxation was not affected by a combination of iberiotoxin (0.1 μM) and apamin (0.1 μM). 5. Ciclazindol (10 μM), an inhibitor of K(V) in rat portal vein smooth muscle, inhibited the L-NOARG/indomethacin-resistant relaxations induced by acetylcholine and A23187, and the relaxations were abolished when ciclazindol (10 μM) was combined with apamin (0.1 μM). 6. Human pial arteries from two out of four patients displayed an L-NOARG/indomethacin-resistant relaxation in response to substance P. This relaxation was abolished in both cases by pretreatment with the combination of charybdotoxin (0.1 μM) and apamin (0.1 (M), whereas each toxin had little effect alone. 7. The results suggest that K(V), but not K(ATP) and BK(Ca), is involved in the EDHF-mediated relaxation in the guinea-pig basilar artery. The synergistic action of apamin and charybdotoxin (or ciclazindol) could indicate that both K(V) and SK(Ca), are activated by EDHF. However, a single type of K-channel, which may be structurally related to K(V) and allosterically regulated by apamin, could also be the target for EDHF.
(Less)
- author
- Petersson, Jesper
LU
; Zygmunt, Peter M.
LU
and Högestätt, Edward D.
LU
- publishing date
- 1997-04-17
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cerebral arteries, Endothelium-derived hyperpolarizing factor, Hyperpolarization, Potassium channels, Vascular endothelium
- in
- British Journal of Pharmacology
- volume
- 120
- issue
- 7
- pages
- 7 pages
- publisher
- Wiley
- external identifiers
-
- scopus:0030893193
- pmid:9105711
- ISSN
- 0007-1188
- DOI
- 10.1038/sj.bjp.0701032
- language
- English
- LU publication?
- no
- id
- 7d51f0a8-7d53-42fc-9860-6d738e54d771
- date added to LUP
- 2019-05-31 21:39:15
- date last changed
- 2024-01-01 08:59:29
@article{7d51f0a8-7d53-42fc-9860-6d738e54d771,
abstract = {{<p>1. In the presence of N(G)-nitro-L-arginine (L-NOARG, 0.3 mM) and indomethacin (10 μM), the relaxations induced by acetylcholine and the calcium (Ca) ionophore A23187 are considered to be mediated by endothelium-derived hyperpolarizing factor (EDHF) in the guinea-pig basilar artery. 2. Inhibitors of adenosine 5'-triphosphate (ATP)-sensitive potassium (K)-channels (K(ATP); glibenclamide, 10 μM), voltage-sensitive K-channels (K(V); dendrotoxin-I, 0.1 μM or 4-aminopyridine, 1 mM), small (SK(Ca); apamin, 0.1 μM) and large (BK(Ca); iberiotoxin, 0.1 μM) conductance Ca-sensitive K-channels did not affect the L-NOARG/indomethacin-resistant relaxation induced by acetylcholine. 3. Synthetic charybdotoxin (0.1 μM), an inhibitor of BK(Ca), and K(V), caused a rightward shift of the concentration-response curve for acetyicholine and reduced the maximal relaxation in the presence of L-NOARG and indomethacin, whereas the relaxation induced by A23187 was not significantly inhibited. 4. A combination of charybdotoxin (0.1 μM) and apamin (0.1 μM) abolished the L-NOARG/indomethacin-resistant relaxations induced by acetylcholine and A23187. However, the acetylcholine-induced relaxation was not affected by a combination of iberiotoxin (0.1 μM) and apamin (0.1 μM). 5. Ciclazindol (10 μM), an inhibitor of K(V) in rat portal vein smooth muscle, inhibited the L-NOARG/indomethacin-resistant relaxations induced by acetylcholine and A23187, and the relaxations were abolished when ciclazindol (10 μM) was combined with apamin (0.1 μM). 6. Human pial arteries from two out of four patients displayed an L-NOARG/indomethacin-resistant relaxation in response to substance P. This relaxation was abolished in both cases by pretreatment with the combination of charybdotoxin (0.1 μM) and apamin (0.1 (M), whereas each toxin had little effect alone. 7. The results suggest that K(V), but not K(ATP) and BK(Ca), is involved in the EDHF-mediated relaxation in the guinea-pig basilar artery. The synergistic action of apamin and charybdotoxin (or ciclazindol) could indicate that both K(V) and SK(Ca), are activated by EDHF. However, a single type of K-channel, which may be structurally related to K(V) and allosterically regulated by apamin, could also be the target for EDHF.</p>}},
author = {{Petersson, Jesper and Zygmunt, Peter M. and Högestätt, Edward D.}},
issn = {{0007-1188}},
keywords = {{Cerebral arteries; Endothelium-derived hyperpolarizing factor; Hyperpolarization; Potassium channels; Vascular endothelium}},
language = {{eng}},
month = {{04}},
number = {{7}},
pages = {{1344--1350}},
publisher = {{Wiley}},
series = {{British Journal of Pharmacology}},
title = {{Characterization of the potassium channels involved in EDHF-mediated relaxation in cerebral arteries}},
url = {{http://dx.doi.org/10.1038/sj.bjp.0701032}},
doi = {{10.1038/sj.bjp.0701032}},
volume = {{120}},
year = {{1997}},
}