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- Title
Characterization of a charybdotoxin-sensitive intermediate conductance Ca[sup2+]-activated K[sup+] channel in porcine coronary endothelium: relevance to EDHF.
- Authors
Bychkov, Rastislav; Burnham, Matthew P.; Richards, Gillian R.; Edwards, Gillian; Weston, Arthur H.; Félétou, Michel; Vanhoutte, Paul M.
- Abstract
1 This study characterizes the K[SUP+] channels(s) underlying charybdotoxin-sensitive hyperpolarization of procine coronary artery endothelium. 2 Two forms of current-voltage (I/V) relationship were evident in whole-cell patch-clamp recordings of freshly-isolated endothelial cells. In both cell types, iberiotoxin (100 nM) inhibited a current active only at potentials over +50 mV. In the presence of iberiotoxin, charybdotoxin (100 nM) produced a large inhibition in 38% of cells and altered the form of the I/V relationship. In the remaining cells, charybdotoxin also inhibited a current but did not alter the form. 3 Single-channel outside-out patch recordings revealed a 17.1 ± 0.4 pS conductance. Pipette solutions containing 100, 250 and 500 nM free Ca[SUP2+] demonstrated that the open probability was increased by Ca[SUP2+]. This channel was blocked by charybdotoxin but not by iberiotoxin or apamin. 4 Hyperpolarization of intact endothelium elicited by substance P (100 nM; 26.1 ± 0.7 mV) were reduced by apamin (100 nM; 17.0 ± 1.8 mV) whereas those to l-ethyl-2-benzimidazolinone (l-EBIO, 600 μM, 21.0 ± 0.3 mV) were unaffected (21.7 ± 0.8 mV). Substance P, bradykinin (100 nM) and l-EBIO evoked charybdotoxin-sensitive, iberiotoxin-insensitive whole-cell perforated-patch current. 5 A procine homologue of the intermediate-conductance Ca[SUP2+]-activated K[SUP+] channel (Ik1) was identified in endothelial cells. 6 In conclusion, porcine coronary artery endothelial cells express an intermediate-conductance Ca[SUP2+]-activated K[SUP+] channel and the Ik1 gene product. This channel is opened by activation of the EDHF pathway and likely mediates the charybdotoxin-sensitive component of the EDHF response.
- Subjects
ENDOTHELIUM; POTASSIUM channels
- Publication
British Journal of Pharmacology, 2002, Vol 137, Issue 8, p1346
- ISSN
0007-1188
- Publication type
Article
- DOI
10.1038/sj.bjp.0705057