Ca(2+)-activated K+ channels in human smooth muscle cells of coronary atherosclerotic plaques and coronary media segments.
The behavior of Ca(2+)-activated K+ channels of large conductance (BKCa) in smooth muscle cells, which were obtained from atherosclerotic plaque material (SMCP) and from media segments (SMCM) of human coronary arteries, were compared using the patch-clamp technique. Voltage-clamp protocols in cell-attached patches revealed the characteristic voltage-dependent activation of BKCa in both cell groups. Single-channel conduction as 216.4 +/- 16.7 pS (n = 6) in SMCP and 199.9 +/- 6.7 pS (n = 6) in SMCM in symmetrical 140 mM K+ solutions. Using outside-out patches, external perfusion with 500 microM tetraethylammonium ions caused a typical "flickery block" of the unitary current. The selective BKCa channel inhibitor iberiotoxin (50 nM) effectively blocked BKCa, channel activity. Comparing BKCa open-state probabilities (P0) at +80 mV in cell-attached patches, a highly significant difference between SMCP (P0 = 0.1438 +/- 0.1301; n = 15) and SMCM (P0 = 0.0093 +/- 0.0044; n = 15; Kruskal-Wallis test, p < 0.001) was found. In contrast to this finding, there was no significant difference in the open-state probability of BKCa, between SMCP (P0 = 0.542 +/- 0.0237; n = 9) and SMCM (P0 = 0.0472 +/- 0.0218; n = 10; p = n.s.) using inside-out patches. The results show an interesting difference in the behavior of large conductance Ca(2+)-activated K+ channel in SMCP compared to SMCM with a significantly higher channel activity in human smooth muscle cells obtained from coronary atherosclerotic plaque material. This finding may indicate an important functional role of BKCa channels in the development of atherosclerosis.
Wiecha
J
J
Department of Cardiology, University Hospital of Giessen, Germany.
Schläger
B
B
Voisard
R
R
Hannekum
A
A
Mattfeldt
T
T
Hombach
V
V
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014118:Toxins, Biological / Q000494:pharmacology
D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014118:Toxins, Biological; D019789:Tetraethylammonium; C064719:iberiotoxin; D002118:Calcium